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79 publications mentioning hsa-mir-376a-2

Open access articles that are associated with the species Homo sapiens and mention the gene name mir-376a-2. Click the [+] symbols to view sentences that include the gene name, or the word cloud on the right for a summary.

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[+] score: 259
Knock-down of MALAT1 upregulated MIR376A, while overexpression of MIR376A inhibited MALAT1 expression in vitro, suggesting a direct association between MALAT1 and MIR376A. [score:12]
Figure 7Regulation of TGFA by manipulation of MALAT1 and MIR376A in human OS cells and TGFA as a direct target of MIR376A(A) assay showed that the expression of TGFA was downregulated by MIR376A overexpression in both Saos2 and MG63 cell lines. [score:11]
Upregulation of TGFA expression in osteosarcoma tissues and cells and its correlation with MIR376A and MALAT1 TGFA is a direct target of MIR376C, one of the MIR376 family members that regulate OS cell growth [18]. [score:10]
Figure 5Upregulation of TGFA expression in osteosarcoma tissues and cells and its correlation with MIR376A and MALAT1(A) Expression of TGFA mRNA was upregulated in tumor tissues compared with adjacent normal tissues. [score:10]
We found that MIR376A expression was downregulated in OS tissues, and MIR376A overexpression inhibited OS cell growth and proliferation. [score:10]
Regulation of TGFA by MALAT1 and MIR376A in human OS cells and TGFA as a direct target of MIR376A TGFA expression was negatively correlated with MIR376A but positively correlated with MALAT1 expression (Figure 5B and 5C). [score:9]
Knockdown of MALAT1 caused upregulation of MIR376A (Figure 4B), whereas MIR376A overexpression resulted in decreased MALAT1 expression compared with the MIR376A-NC group (Figure 4C). [score:8]
Figure 3 MIR376A suppression of osteosarcoma cell growth in vitro(A) Expression of MIR376A was downregulated in OS tissues compared with adjacent normal tissues. [score:7]
Inverse correlation of MIR376A and MALAT1 expression in osteosarcoma tissues and direct interaction between MIR376A and the 3′UTR of MALAT1 in vitroAccording to previous studies, MIR376 family members play a suppressive role in OS [18, 19]. [score:6]
TGFA was downregulated by overexpression of MIR376A as demonstrated by western blot (Figure 7A). [score:6]
Figure 4Inverse association of MIR376A with MALAT1 expression in osteosarcoma tissues and direct interaction between MIR376A and the 3′UTR of MALAT1 in vitro(A) An inverse correlation between MALAT1 and MIR376A expression was observed. [score:6]
Moreover, overexpression of MIR376A or knockdown of MALAT1 both resulted in markedly reduced TGFA expression. [score:6]
Upregulation of TGFA expression in osteosarcoma tissues and cells and its correlation with MIR376A and MALAT1. [score:6]
TGFA expression was negatively correlated with MIR376A but positively correlated with MALAT1 expression (Figure 5B and 5C). [score:5]
We showed that TGFA expression correlated with MALAT1 and MIR376A expression in OS. [score:5]
Together, these data suggested that MIR376A expression is negatively correlated with MALAT1 expression in OS. [score:5]
Thus, our data indicate that MALAT1 may promote OS cell growth through inhibition of MIR376A and by targeting TGFA. [score:5]
TGFA is a direct target of MIR376C, one of the MIR376 family members that regulate OS cell growth [18]. [score:5]
It has been reported that TGFA regulates OS cell growth as a direct target of MIR376C, one of the MIR376 family members [18]. [score:5]
These results support a direct correlation of MALAT1, MIR376A, and TGFA expression in the regulation of OS cell growth. [score:5]
Thus, there was an inverse correlation between TGFA and MIR376A (Figure 5C), whereas TGFA expression was positively correlated with MALAT1 expression (Figure 5D). [score:5]
MIR376A suppression of osteosarcoma cell growth in vitro MIR376A was recently shown to function as a tumor suppressor in several cancers [16, 17]. [score:5]
Regulation of TGFA by MALAT1 and MIR376A in human OS cells and TGFA as a direct target of MIR376A. [score:5]
Our results support a MALAT1/ MIR376A/ TGFA axis in OS tumor progression whereby MALAT1 promotes OS cell growth through inhibition of MIR376A and targeting of TGFA. [score:5]
Regulation of TGFA by manipulation of MALAT1 and MIR376A in human OS cells and TGFA as a direct target of MIR376A. [score:5]
To further determine their relationship, we measured the expression of TGFA in response to MIR376A overexpression and MALAT1 knockdown in human OS cells. [score:4]
There was no reduction of reporter activity in cells co -transfected with MIR376A and the mut- TGFA reporter, suggesting that MIR376A directly inhibits TGFA through interaction with its 3′-UTR (Figure 7D). [score:4]
Inverse association of MIR376A with MALAT1 expression in osteosarcoma tissues and direct interaction between MIR376A and the 3′UTR of MALAT1 in vitro. [score:4]
s on the MIR376A overexpressing Saos2 and MG63 cells revealed that overexpression of MIR376A reduced cell growth when compared with the MIR376A-NC group (Figure 3C and 3D). [score:4]
To investigate whether MIR376A correlates with MALAT1 in regulation of OS cell growth, we performed expression analysis and found an inverse correlation between MALAT1 and MIR376A expression in OS tissues (Figure 4A). [score:4]
Inverse correlation of MIR376A and MALAT1 expression in osteosarcoma tissues and direct interaction between MIR376A and the 3′UTR of MALAT1 in vitro. [score:4]
There was a direct interaction between MIR376A and TGFA, with MIR376A regulating TGFA via a 5-bp putative binding site within its 3′-UTR. [score:3]
MIR376A suppression of osteosarcoma cell growth in vitro. [score:3]
To understand the mechanisms of MALAT1 in the OS tumorigenesis, we detected a direct interaction between MIR376A and both MALAT1 and TGFA, suggesting a novel mechanism of MALAT1, MIR376A, and TGFA in the regulation of OS cell growth. [score:3]
These results provide direct evidence of a MALAT1- MIR376A interaction in the regulation of OS tumorigenesis. [score:3]
In conclusion, we found differential expression of MALAT1, MIR376A and TGFA in OS cell lines and tissues. [score:3]
MIR376A is a tumor-suppressive microRNA associated with multiple cancers, including hepatocellular carcinoma, melanoma, and glioblastoma [16, 17, 24, 25]. [score:3]
MIR376A mimics were then transfected into Saos2 and MG63 cells to achieve MIR376A overexpression as confirmed by real-time qPCR (Figure 3B). [score:3]
We also showed that TGFA expression is positively correlated with MALAT1 but negatively correlated with MIR376A. [score:3]
These data demonstrated that MIR376A inhibited OS cell growth and proliferation. [score:3]
According to previous studies, MIR376 family members play a suppressive role in OS [18, 19]. [score:3]
MIR376A was recently shown to function as a tumor suppressor in several cancers [16, 17]. [score:3]
MIR376A was downregulated in OS tissues compared with adjacent normal tissues (Figure 3A). [score:3]
We also observed an inverse correlation between MALAT1 and MIR376A expression in OS tissues. [score:3]
We found a negative correlation between MIR376A and MALAT1 or TGFA expression. [score:3]
In support of this, we found that MIR376A may regulate MALAT1 via a putative binding site within its 3′UTR. [score:2]
The mut- MALAT1 contained a 6 bp mutation in the putative MIR376A binding site within the MALAT1 3′-UTR (Figure 4D). [score:2]
MIR376A maps to the 14q32 locus, which harbors a cluster of miRNAs that are known to regulate proliferation, apoptosis, migration, and invasion of several cancers [24, 26]. [score:2]
These results suggested a direct interaction between MIR376A and MALAT1 via the 6-bp putative MIR376A binding site within the 3′UTR of MALAT1. [score:2]
More importantly, there was a direct interaction between MIR376A and MALAT1 or TGFA. [score:2]
To investigate whether MIR376A repression of OS cell growth is through inhibition of TGFA, we generated two TGFA-containing luciferase reporter constructs: wt- TGFA and a mut- TGFA which contained a 5 bp mutation in a putative MIR376A binding site within its 3′-UTR (Figure 7C). [score:2]
In addition, MIR 376A overexpression reduced DNA synthesis in both Saos2 and MG63 cells compared with the MIR376A-NC group, as indicated by BrdU incorporation (Figure 3E and 3F). [score:2]
To investigate whether TGFA associates with MIR376A and MALAT1 and plays a role in OS, we examined TGFA mRNA and protein expression in OS tissues. [score:1]
These luciferase reporter constructs were co -transfected into Saos2 cells with MIR376A-NC or MIR376A mimics. [score:1]
To investigate the role of MIR376A in OS, we first examined MIR376A expression in OS tissues. [score:1]
No reduction of reporter activity was shown in cells co -transfected with MIR376A and the mut- TGFA reporter. [score:1]
The cells were then transfected with 100 nM MIR376A mimics, MIR376A-NC, si-NC/si- MALAT1 or si-NC/si- TGFA. [score:1]
In this study, we measured expression of MALAT1, MIR376A and TGFA in OS cell lines and tissues. [score:1]
The repression of luciferase activity by MIR376A was not seen in cells transfected with mut- MALAT1 (Figure 4E). [score:1]
Repression of luciferase activity by MIR376A was not shown in cells transfected with mut- MALAT1. [score:1]
These wt- MALAT1 and mut- MALAT1 vectors and MIR376A-NC or MIR376A mimics were co -transfected into Saos2 cells. [score:1]
Luciferase activity of the wt- MALAT1 vector was reduced in cells co -transfected with MIR376A mimics. [score:1]
When cells reached 40–60% confluence, 150-nM MIR376A mimics or negative control (NC) was transfected using Lipofectamine™ 2000 transfection reagent (Invitrogen, USA) following the protocol recommended by the manufacturer. [score:1]
Their sequences were as follows: 5′-UUCUCCGAAC GUGUCACGUT T-3′ (sense) and 5′-ACGUGACACG UUCGGAGAAT T-3′ (antisense) for NC and 5′-AUCAUAGAGG AAAAUCCACG U-3′ (sense) and 5′-GUGGAUUUUC CUCUAUGAUU U-3′ (antisense) for MIR376A mimics. [score:1]
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[+] score: 202
Other miRNAs from this paper: hsa-mir-376a-1, hsa-mir-376b
To demonstrate that miR-376a(e) specifically, controls the expression of HLA-E we overexpressed miR-376a(e), miR-376a or a control miRNA in BJAB cells (we selected BJAB cells because they express HLA-E). [score:7]
As previously reported [19], a moderate, yet statistically significant reduction in MICB expression was observed in cells transduced with miR-376a (Fig. 4b, left, quantified in Fig. 4c), while the expression of other NKG2D ligands expressed on R KO cells was not affected (Fig. S3a). [score:7]
Finally, qRT-PCR analysis of the relative abundance of HLA-E mRNA in cells transduced with miR-376a(e) demonstrated no effect as compared to control cells (Fig. 5h), suggesting that miR-376a(e) represses HLA-E expression through translational inhibition. [score:6]
We continue to show that the edited-miR-376a then downregulates the inhibitory molecule HLA-E, and by doing so promotes the elimination of HCMV infected cells by NK cells. [score:6]
To demonstrated that miR-376a(e) regulates HLA-E expression by direct binding to the predicted sites (Fig. 5a), we generated reporters bearing single (mut187 or mut1342) and double (mut187 and mut1342, named Dmut) mutations in the predicted binding sites (Fig. S6). [score:6]
We further show that increased editing of miR-376a is observed upon HCMV infection and that the edited miR-376a (miR-376a(e)), downregulates the expression of HLA-E to render infected cells susceptible to elimination by NK cells. [score:6]
The expression of HLA-E was induced following infection however in HCMV infected HFF cells transduced with the anti-miR-376a(e) sponge the expression of HLA-E was significantly higher than that in the control cells (Fig. 6c, red histogram, quantified in Fig. S7b). [score:5]
Irrespective of the donors' NKG2C [+] NK cells percentage, the expression of the anti-miR-376a(e)-sponge which led to increased levels of HLA-E (Fig. 6c), resulted in inhibition of NK function and reduced killing of infected cells (Fig. 7d). [score:5]
Although R KO cell already express ADAR1 (Fig. S4a) overexpression of ADAR-p110 (black histograms), moderately elevated the levels of MICB only (Fig. 4f, quantified in Fig. 4g), probably due to reduced miR-376a levels. [score:5]
We also show that HLA-E, which was not known previously to be regulated by miRNAs, is downregulated by miR-376a(e) and that this consequently leads to the elimination of the HCMV infected cells by NK cells. [score:5]
Thus, we concluded as we previously reported [21], [38] that even a moderate change in MICB expression that is mediated by miR-376a is sufficient to affect NK cytotoxicity and that miR-376a(e) does not affect MICB expression. [score:5]
While expression of miR-376a did not affect the reporter's activity (Fig. 5f), repression was observed in cells expressing miR-376a(e) (Fig. 5g). [score:5]
Thus we concluded that following HCMV infection ADAR-p110 is induced, miR-376a is edited and that the edited miRNA, miR-376a(e), regulates the expression of HLA-E. After we demonstrated that antagonizing ADAR1-p110 and miR-376a(e) affects HLA-E during HCMV infection we next wanted to test the functional implications of these findings. [score:4]
Thus, we concluded that editing of miR-376a abolishes its ability to regulate the expression of MICB. [score:4]
Together, these results demonstrate the dominance of the inhibitory signal generated by NKG2A in controlling NK cell activity and the importance of the regulation of HLA-E by miR-376a(e) during HCMV infection. [score:4]
Interestingly, we demonstrated in the past that miR-376a down regulates the expression of the stress -induced ligand MICB [19]. [score:4]
Thus we concluded that following HCMV infection ADAR-p110 is induced, miR-376a is edited and that the edited miRNA, miR-376a(e), regulates the expression of HLA-E. (a) HFF and ARPE-19 cells were transfected with the indicated reporter plasmids and were infected with AD169 or TB40/E, respectively. [score:4]
MiR-376a(e) directly binds the 3′ UTR of HLA-E and regulates its expression. [score:4]
We next wondered whether miR-376a(e) might regulate the expression of immune genes that are known to be affected during HCMV infection. [score:4]
These observations were supported by NK killing assays against the transduced R KO cells in which the expression of miR-376a lead to reduced NK cell killing while expression of miR-376a(e) had no effect (Fig. 4e). [score:4]
Additionally we show that miR-376a is edited during HCMV infection and that knockdown or over expression of ADAR1-p110 affects miR-376a editing, suggesting that ADAR1-p110 controls the editing of miR-376a during HCMV infection. [score:4]
Thus, we next tested whether miR-376a(e) is able to control the expression of MICB. [score:3]
Figure S8 Antagonizing miR-376a or miR-376a(e) does alters MICB expression during HCMV infection. [score:3]
Our current results are in line with these observations as we show that although the proportion of NKG2C [+] cells is higher in HCMV [pos] individuals, the outcome of neutralizing miR-376a(e) during infection (which leads to increased HLA-E levels) is inhibition of NK cell function irrespective of the donors' serotype. [score:3]
Because the editing of miR-376a occurs in its seed region, it is expected (as previously reported [22]) that the target spectrum of miR-376a(e) will be different than that of miR-376a. [score:3]
We analyzed the levels of miR-376a(e) by small RNA next generation sequencing and observed increased levels of miR-376a(e) specifically in ADAR1-p110 -expressing HFF cells (Fig. 3g). [score:3]
Thus, we concluded that miR-376a(e) directly binds the 3′ UTR of HLA-E at the predicted binding sites and that both binding sites are necessary for the regulation of HLA-E by miR-376a(e). [score:3]
Because miR-376a(e) does not control the expression of MICB (Fig. 4) and since we showed that ADAR1-p110 is strongly induced specifically upon HCMV infection (Figs. 1 and 2) leading to increase levels of miR-376a(e) (Fig. 3). [score:3]
We initially validated that the miR-376a(e) binding sites in the 3′ UTR of HLA-E are targeted during HCMV infection. [score:3]
Interestingly, one of the miRNA that was shown by us to target MICB, miR-376a [19], is known to be edited by ADAR enzymes [22]. [score:3]
To validate that miR-376a(e) regulates HLA-E by directly binding to the predicted binding sites, we fused the 3′ UTR of HLA-E downstream to a Firefly reporter. [score:3]
MiR-376a(e) regulates HLA-E expression during HCMV infection. [score:3]
In agreement with our above results in which we showed that miR-376a(e) does not control the expression of MICB (Fig. 4b), only the anti-miR-376a sponge had an effect on the levels of MICB in uninfected HFF cells (Fig. 7a). [score:3]
We next wanted to demonstrate that miR-376a(e) specifically controls the endogenous expression of HLA-E during HCMV infection. [score:3]
RNA editing of miR-376a abolishes its regulation of MICB. [score:2]
Editing of miR-376a abolishes its ability to regulate MICB. [score:2]
We also demonstrated that miR-UL112 acts synergistically with the cellular miR-376a (that also regulates MICB), and that this leads to reduce killing of the infected cells [19]. [score:2]
In contrast, HLA-E levels were initially increased in HCMV infected cells (GFP [pos], Fig. 8e and 8f), probably because of the viral UL40 protein, but were then reduced as infection prolonged (Fig. 8g and 8h), probably due to the editing of miR-376a(e) which results in the down regulation of HLA-E. 10.1371/journal. [score:2]
In contrast, HLA-E levels were initially increased in HCMV infected cells (GFP [pos], Fig. 8e and 8f), probably because of the viral UL40 protein, but were then reduced as infection prolonged (Fig. 8g and 8h), probably due to the editing of miR-376a(e) which results in the down regulation of HLA-E. 10.1371/journal. [score:2]
We also performed the reciprocal experiments in which we transduced HFF cells with miR-376a(e) (which leads to the down regulation of HLA-E). [score:2]
Dual luciferase assays were performed in cells transduced with lentiviruses expressing miR-376a(e), miR-376a or control miRNA and then transfected with the Firefly reporter. [score:2]
HLA-E is regulated by miR-376a(e). [score:2]
The regulation of HLA-E by miR-376a(e) during infection affects NK cell cytotoxicity. [score:2]
Because we demonstrated that ADAR1-p110 and editing of miR-376a are induced specifically following HCMV infection and since we showed that miR-376a(e) regulates HLA-E, we next tested whether miR-376a(e) controls HLA-E during HCMV infection. [score:2]
To demonstrate that ADAR1-p110 has a role in the editing of miR-376a during HCMV infection we knocked down ADAR1. [score:2]
Figure S6 Mutations in the 3′UTR of HLA-E. Alignment of miR-376a(e) to the mutated 3′ UTRs of HLA-E which were fused downstream to the Firefly luciferase reporter. [score:2]
Therefore, when TB40/E is used editing of miR-376a has no effect on HLA-E levels and we could nicely observe that the infected cells were less susceptible due to the viral and cellular miRNAs operating to reduce NK cell killing [19]. [score:1]
This is because the anti-miR-376a(e) sponge does not antagonize MICB (Fig. 7a) and because, as we have previously shown the anti-miR-376a sponge by itself is not sufficient to alter the levels of MICB during HCMV infection due to a synergistic interaction with the viral miR-UL112 [19]. [score:1]
Reviewing the reads mapping to miR-376a (MIMAT0000729), a pileup of the supported alleles and their sequencing quality was produced using SAMtools [52]. [score:1]
MiR-376a was shown to be one of the primary miRNAs that undergo editing by ADAR proteins [22]. [score:1]
1003963.g003 Figure 3(a) The rate of miR-376a(e) in HFF cells either mock treated or HCMV infected was determined by next generation small RNA deep sequencing. [score:1]
1003963.g004 Figure 4(a) Alignment of miR-376a (black top) and miR-376a(e) (black bottom) to the 3′ UTR of MICB (grey). [score:1]
MiR-376a(e) -mediated regulation of HLA-E during infection affects NK cell cytotoxicity. [score:1]
ADAR1-p110 is involved in the editing of miR-376a. [score:1]
For this we generated an anti-miRNA sponge construct, consisting of six adjacent binding sites for miR-376a(e), fused downstream to an eGFP cassette. [score:1]
Indeed reduced HLA-E levels were observed only in cells transduced with miR-376a(e), whereas the unedited miR-376a or control-miRNA had no effect (Fig. 5d, quantified in Fig. 5e). [score:1]
1003963.g007 Figure 7(a) FACS analysis of MICB levels on HFF cells transduced either with an anti-miR-376a sponge (black histogram), or an anti-miR-376a(e) sponge (grey histogram). [score:1]
The mouse orthologous protein of HLA-E, Qa-1b, does not contain predicted binding sites for the mouse orthologue of miR-376a(e). [score:1]
Importantly, increased levels of HLA-E following transduction of HFF cells with the anti-miR-376a(e) sponge, were observed following infection with AD169, Merlin, CI and the TB40/E strain (Fig. 6d, quantified in 6e). [score:1]
html) to screen for possible miR-376a(e) binding sites in 3′UTR of various related genes. [score:1]
In contrast, during HCMV infection only the anti-miR-376a(e) sponge led to increase levels of HLA-E (Fig. 7b). [score:1]
In contrast, little or no change in MICB levels was observed in cells transduced with miR-376a(e) (Fig. 4b right, quantified in Fig. 4c). [score:1]
Next, HFF cells transduced either with the anti-miR-376a(e)-sponge or with a control sponge, were infected with HCMV and subjected to killing by NK cells derived from HCMV [neg] and HCMV [pos] donors. [score:1]
MiR-376a(e) regulation of HLA-E during HCMV infection. [score:1]
As miR-376a and miR-376a(e) differ in only one nucleotide, it is impossible to distinguish between the two miRNAs by qRT-PCR. [score:1]
All mutant reporters abolished the miR-376a(e) -mediated repression (Fig. 5g). [score:1]
Hence we performed next generation small RNA sequencing on uninfected and HCMV infected HFF cells and observed an increase in miR-376a(e) levels following infection (Fig. 3a). [score:1]
HFF cells transduced with an anti-miR-376a sponge (red histogram), anti-miR-376a sponge (back histogram) or a control sponge (filled dark grey histogram) were infected with HCMV and MICB levels were assessed by FACS 48 hrs after infection. [score:1]
Thus, to test the functional significance of the miR-376a(e) -mediated control of HLA-E during infection we isolated NK cells from four HCMV [neg] and four HCMV [pos] donors (Fig. 7c). [score:1]
S1: Supporting Methods) or with an anti-miR-376a(e) sponge, and then infected with HCMV. [score:1]
One of the top candidates was HLA-E, which was predicted to have two binding sites for miR-376a(e) in its 3′ UTR (Fig. 5a), yet no such sites were predicted for the unedited miR-376a. [score:1]
ADAR1-p110 affects the editing of miR-376a. [score:1]
Moreover, no sites for the mouse orthologue of miR-376a(e) (mmu-miR-376b(e)) were predicted in the 3′UTR of the mouse orthologue of HLA-E, Qa-1b. [score:1]
1003963.g005 Figure 5(a) Alignment of the two predicted binding sites of miR-376a(e) (in black) in the 3′ UTR of HLA-E (grey). [score:1]
Here we show that editing of miR-376a renders the infected cells susceptible to NK cell cytotoxicity. [score:1]
Indeed, miR-376a(e) does not have a full seed base-pairing with the 3′UTR of MICB (Fig. 4a). [score:1]
After we demonstrated that antagonizing ADAR1-p110 and miR-376a(e) affects HLA-E during HCMV infection we next wanted to test the functional implications of these findings. [score:1]
R KO cells were transduced with lentiviral vectors encoding miR-376a, miR-376a(e), or a control miRNA. [score:1]
We find that following HCMV infection a specific ADAR1 isoform, ADAR1-p110, is strongly induced and that in addition editing of miR-376a is also increases. [score:1]
Thus to demonstrate the functional effect miR-376a(e) has on NK killing of HCMV infected HFF cells we utilize the sponges mentioned above and for that we initially verified the sponge's specificity. [score:1]
So far we showed that ADAR1-p110 is induced specifically during HCMV infection and that ADAR1-p110 can edit miR-376a. [score:1]
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[+] score: 124
Introduction of the IGF1R-3'UTR-luciferase vector into mir-376a -transfected or mir-376c -transfected cells led to a significant ~83% and ~65% decrease in the level of luciferase expression relative to the same cells following introduction with a control luciferase vector, respectively, indicating that the stable expression of both miRNAs leads to further significant down-regulation on the 3'UTR of IGF1R (Figure  4D), thus establishing IGF1R as a target of both mir-376a and mir-376c. [score:10]
We therefore decided to focus on other miRNAs whose expression was shown to be down-regulated but not entirely absent in melanoma and as a first step generated melanoma cell lines that ectopically express either mir-376a or mir-376c (Figure  3A). [score:8]
To assess whether the down-regulation of IGF1R by mir-376a and mir-376c could account for the observed biological phenotype in these cells, IGF1R was pharmacologically inhibited using the commercially-available IGF1R inhibitor AG-1024 [26]. [score:8]
Our results suggest that down-regulation of mir-376a and mir-376c may contribute to IGF1R over -expression and to aberrant negative regulation of this signaling pathway in melanoma, thus promoting tumorigenesis and metastasis. [score:7]
In our experimental system, IGF1R levels were higher in melanoma cell lines than in normal melanocytes, and the ectopic expression of mir-376a and mir-376c led to down-regulation of the receptor. [score:6]
The work presented here demonstrates that mir-376a and mir-376c negatively regulate IGF1R, and suggests that aberrations in this regulatory mechanism, in the form of down-regulation of mir-376a/c, take part in melanoma progression and metastasis. [score:6]
Stable over -expression of mir-376a and mir-376c, two miRNAs from this cluster that could be re-expressed following epigenetic manipulation, led to modest growth retardation and to a significant decrease in migration in-vitro. [score:5]
Pharmacological inhibition of IGF1R pheno-copied the decrease in migration seen following mir-376a and mir-376c over -expression, suggesting that down-modulation of the IGF1R signaling pathway may be responsible for the observed anti-migratory effect of these miRNAs in melanoma cell lines. [score:5]
IGF1R inhibition by AG-1024 pheno-copied the decrease in migration seen following over -expression of either mir-376a or mir-376c using the same experimental system, in a dose -dependent manner (Figure  4E). [score:5]
Four of these miRNAs (namely mir-127-3p, mir-136, mir-376a and mir-376c) were shown to be down-regulated but not completely silenced in nevi and melanomas. [score:4]
Indeed, stable expression of mir-376a and mir-376c in melanoma cells led to a decrease in IGF1R and protein, and a luciferase reporter assay indicated that the 3'UTR of IGF1R is a target of both mir-376a and mir-376c. [score:4]
Four of these five miRNAs (mir-127-3p, mir-136, mir-376a and mir-376c) were found to be down-regulated but not entirely silenced in nevi and melanoma (Additional file 2). [score:4]
In order to determine whether IGF1R is a direct target of miR-376a/c, we used a commercial plasmid containing the first ~2800 nucleotides of the IGF1R 3'UTR cloned downstream to the luciferase reporter gene. [score:4]
Following selection, the stable ectopic expression of mir-376a/c was repeatedly assessed using qRT-PCR. [score:3]
The administration of AG-1024 to melanoma cells over -expressing either mir-376a or mir-376c did not lead to a further decrease in their migration (results not shown), suggesting that the IGF1R axis could not be further modulated to decrease migration. [score:3]
Figure 4 Establishment of IGF1R as a target of mir-376a/c. [score:3]
Stable expression of mir-376a or mir-376c led to a decrease in IGF1R levels both at the and at the protein levels (Figure  4C). [score:3]
Luciferase reporter assays indicate that, as bioinformatically predicted, mir-376a and mir-376c directly target IGF1R. [score:3]
This vector was then introduced into melanoma cells over -expressing mir-376a, mir-376c or a control vector (designated pTER). [score:3]
AG-1024 did not lead to decreased cellular proliferation in either the control cells or the cells over -expressing mir-376a or mir-376c, suggesting that the modest effect of these miRNAs on cellular growth is mediated through different mechanisms. [score:3]
Ectopic expression of mir-376a and mir-376c had a modest yet significant effect on cell growth, but a profound effect on cellular migration in-vitro. [score:3]
Nonetheless, the inhibition of IGF1R by mir-376a and mir-376 has not been described before. [score:3]
We provide data showing that re -expression of mir-376a and mir-376c, two miRNAs from this cluster, lead to attenuation of melanoma proliferation and migration. [score:3]
Cells over -expressing either mir-376a or mir-376c exhibited attenuated growth relative to pTER -transfected control cells (Figure  3B). [score:3]
Re -expression of two miRNAs from this cluster, namely mir-376a and 376-c, attenuate melanoma proliferation and migration. [score:3]
Figure 3 The effect of stable expression of mir-376a and mir-376c on the proliferation and migration of melanoma cells. [score:3]
Bioinformatic analysis using several web -based tools showed that miRNA-376a and miRNA-376c have putative binding sites at the 3'UTR of IGF1R (Figure  4A), a tyrosine kinase receptor long known to be implicated in melanoma tumorigenesis and progression [23]. [score:1]
Whereas pTER -transfected control melanoma cells exhibited a time -dependent migration through the membrane, the mir-376a and mir-376c transfected cells showed almost no migration through the membrane within a 24 h period (Figure  3E). [score:1]
obtained with the more sensitive method of qRT-PCR verified that mir-376a, mir-376c and mir-136 can be significantly induced following treatment with epigenetic modifiers in most of the melanoma cell lines (Figure  2E and results not shown). [score:1]
Interestingly, out of all 65 chromosome-14-miRNAs assessed in four melanoma cell lines, only five miRNAs were shown to be induced in any of the cell lines: mir-127-3p, mir-137, mir-376a (also designated mir-376a-3p), mir-376c and mir-485-3p. [score:1]
Theoretically, mir-376a could generate a stronger interaction with the IGF1R 3'UTR through additional nucleotide pairing beyond the "seed" sequence [24, 25] (Figure 4A). [score:1]
It is to note that there are two miRNA genes, mir-376a-1 and mir-376a-2, coding identical mature miRNAs, that are indistinguishable. [score:1]
The putative binding site of mir-376c is classified as ‘7mer-8mer binding’, and that of mir-376a is classified as ‘8mer binding’. [score:1]
Both mir-376a and mir-376c pre-miRNAs were cloned into the pTER plasmid [47, 48]. [score:1]
Mir-376a and mir-376c transfected cells showed significantly attenuated migration through a transwell membrane 24 hours after seeding relative to pTER -transfected control cells (Figure  3D). [score:1]
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4
[+] score: 119
Therefore, the post-transcriptional control of GRP78 by rno-miR-376a has a significant impact on the regulation of GRP78 protein expression and not gene expression, which is evident by the lack of GRP78 transcriptional regulation. [score:7]
To identify the rno-miR-376a -binding site at the 3′-end of GRP78 mRNA, we generated a direct-match miRNA target site and cloned the insert into the multiple cloning site in the luciferase reporter vector from the pMIR-REPORT miRNA Expression Reporter Vector System (Applied Biosystems). [score:6]
Therefore, we measured the expression of GRP78 mRNA, rno-miR-144, rno-miR-376a, and rno-miR-451 using real-time RT-PCR to examine their expression patterns in the context of LHR downregulation (Fig. 1). [score:6]
Effects of Pre-miR-376a (precursor) and Anti-miR-376a (inhibitor) transfection on rat GRP78 mRNA expression in primary rat granulosa cells. [score:5]
In a similar manner, rno-miR-144 and rno-miR-376a expression peaked 12 h after the hCG treatment, and rno-miR-451 expression peaked 24 h after the hCG treatment. [score:5]
The results presented in this study (Fig. 4 and Fig. 5) demonstrate that rno-miR-376a decreases GRP78 protein production by translational repression without altering GRP78 mRNA levels and that the transfection of rno-miR-376a into granulosa cells repressed protein expression by approximately three-fold (Fig. 5). [score:5]
Thus, we believe that rno-miR-376a is involved in the regulation of GRP78 expression in the ovary. [score:4]
Combined with the MicroCosm analysis of miRNA targets, which revealed that 44 miRNAs can bind to the 3′-UTR of GRP78 mRNA, we speculate that multiple miRNAs may constitute a network that is involved in the regulation of GRP78 mRNA, whereas rno-miR-376a is solely identified to be evoked by the ovulatory signal. [score:4]
uk/) revealed that rno-miR-144, rno-miR-376a, and rno-miR-451 can bind to the 3′-UTR of GRP78 mRNA (from bp 2439–2459) and negatively regulate GRP78 expression. [score:4]
Rat GRP78 mRNA, rno-miR-376a expression in primary rat granulosa cells induced by FSH. [score:3]
From these, we narrowed the focus to rno-miR-376a based on the results of the in vitro experiments (Fig. 2) since rno-miR-144 and rno-miR-451 was not induced expression by hCG treatment. [score:3]
Rat GRP78 mRNA, rno-miR-144, rno-miR-376a, and rno-miR-451 expression in primary rat granulosa cells induced by FSH and hCG. [score:3]
The following oligonucleotides were used in this studies: (1) miR-376a, 5′-aatgcactagtACGAGGATTTTCCTCTACGATaagcttaatgc-3′ and 5′-gcattaagcttATCGTAGAGGAAAATCCTCGTactagtgcatt-3′, and (2) rno-miR-376a -binding site sequence at the 3′-end of GRP78 mRNA, 5′-aatgcactagtATGGTAGAAAAAAGTTCCTACaagcttaatgc-3′ and 5′-gcattaagcttGTAGGAACTTTTTTCTACCATactagtgcatt-3′ We transfected HEK293 cells with 200 ng of each vector (pMIR-REPORT luciferase vectors, as described above, and the pMIR-REPORT βgal vector as a control for transfection normalization) and 50 nM precursor or inhibitor using Lipofectamine 2000 Transfection Reagent according to the manufacturer's protocol. [score:3]
The array data along with the bioinformatic analysis provided by MicroCosm Targets, which indicated that several miRNAs bind to the GRP78 mRNA 3′-UTR, led us to focus on rno-miR-144, rno-miR-376a, and rno-miR-451. [score:3]
Time course of rat GRP78 mRNA, rno-miR-144, rno-miR-376a, and rno-miR-451 expression in rat ovaries induced by PMSG and hCG. [score:3]
Moreover, the state of the complementarity between target mRNA and miRNA has been suggested to affect mRNA degradation [34], which is applicable to rno-miR-376a because the introduction of the complete identical sequence of rno-miR-376a into a reporter vector abolished the luciferase activity, whereas the luciferase activity was reduced to 50% using the reporter vector containing the 3′-UTR rno-miR-376a binding site of GRP78 mRNA (Fig. 6). [score:3]
These data demonstrate that the translation of GRP78 was blocked by precursor via a binding site that was the complementary sequence to rno-miR-376a. [score:3]
miR-376a does not affect GRP78 mRNA expression. [score:3]
The cells were incubated with FSH (30 ng/mL) and estradiol (10 nM) for 48 h. Pre-miR-376a (precursor) or Anti-miR-376a (inhibitor) was transfected into the cells, and 30 ng/mL hCG was added 12 h later. [score:3]
In conclusion, the present results demonstrate that the induction of rno-miR-376a production by hCG leads to repression of GRP78 translation. [score:3]
Twenty-four hours after seeding, the cells were incubated with FSH (30 ng/mL) and estradiol (10 nM) for 48 h. The cells were then transfected with Pre-miR-376a (precursor) or Anti-miR-376a (inhibitor) (50 nM each) purchased from Ambion (product IDs: PM10504 and AM10504, respectively) using siPORT NeoFX Transfection Agent according to the manufacturer's protocol. [score:3]
HEK293 cells were prepared, and the cells were transfected with 200 ng of each reporter vector with 50 nM Pre-miR-376a (precursor) or Anti-miR-376a (inhibitor) as described in the. [score:3]
We then examined the effects of rno-miR-376a on GRP78 mRNA levels following the transfection of granulosa cells with either precursor or inhibitor (Fig. 4). [score:3]
The following oligonucleotides were used in this studies: (1) miR-376a, 5′-aatgcactagtACGAGGATTTTCCTCTACGATaagcttaatgc-3′ and 5′-gcattaagcttATCGTAGAGGAAAATCCTCGTactagtgcatt-3′, and (2) rno-miR-376a -binding site sequence at the 3′-end of GRP78 mRNA, 5′-aatgcactagtATGGTAGAAAAAAGTTCCTACaagcttaatgc-3′ and 5′-gcattaagcttGTAGGAACTTTTTTCTACCATactagtgcatt-3′ We transfected HEK293 cells with 200 ng of each vector (pMIR-REPORT luciferase vectors, as described above, and the pMIR-REPORT βgal vector as a control for transfection normalization) and 50 nM precursor or inhibitor using Lipofectamine 2000 Transfection Reagent according to the manufacturer's protocol. [score:3]
miR-376a represses GRP78 translation. [score:3]
GRP78 mRNA and rno-miR-376a expression increased significantly 12 h after the addition of hCG into the culture medium and subsequently decreased, which was consistent with in vivo study (Fig. 1). [score:3]
Transfection with Pre-miR-376a miRNA (precursor) and Anti-miR-376a miRNA (inhibitor). [score:3]
Cells were then incubated with FSH (30 ng/mL) and estradiol (10 nM) for 48 h in the same way as described in Fig. 2. The time after 48 h of incubation with FSH and estradiol was considered “0 h. ” Total RNA was isolated, and rno-miR-376a expression levels was determined using real-time RT-PCR at the indicated time. [score:2]
Total RNA was isolated, and GRP78 mRNA (A), rno-miR-144 (B), rno-miR-376a (C), and rno-miR-451 (D) expression levels were measured using real-time RT-PCR as described in the. [score:1]
miR-376a binds to predicted site of GRP78 3′-UTR. [score:1]
Effects of rno-miR-376a on GRP78 protein in granulosa cells. [score:1]
To identify the rno-miR-376a -binding site in the 3′-UTR of GRP78 mRNA, luciferase reporter vectors were generated as described in the. [score:1]
To confirm the presence of an rno-miR-376a binding site on GRP78 mRNA, we constructed a reporter vector that contained a putative rno-miR-376a binding site sequence (bp 2439–2459) in the 3′-UTR downstream of a Renilla luciferase coding region. [score:1]
One can argue whether this reduction of GRP78 protein by rno-miR-376a has significant meaning for physiological functions in the ovary. [score:1]
The amount of rat GRP78 mRNA, rno-miR-144, rno-miR-376a, and rno-miR-451 in the hCG 0 h group was set at 1. Data were normalized to 18S rRNA (for GRP78 mRNA) and 4.5S RNA(H) (for rno-miR-144, rno-miR-376a, and rno-miR451) levels in each sample and represent the mean ±SE of three independent experiments. [score:1]
This result indicates that rno-miR-376a binds to the 3′-end of GRP78 mRNA from bp 2439–2459 in the 3′-UTR. [score:1]
The luciferase activity in the cells transfected with the reporter vector containing the putative rno-miR-376a binding site was reduced by approximately 50% 24 h after the cells were transfected with precursor. [score:1]
The amounts of rno-miR-376a in the 0 h group were set at 1. Data were normalized for 4.5S RNA(H) levels in each sample and represent the mean ±SE of 3 independent experiments. [score:1]
0108997.g006 Figure 6s for the identification of the rno-miR-376a -binding site in the 3′-UTR of GRP78 mRNA. [score:1]
To verify the effect of the miRNA transfection, we generated a reporter vector that included the whole miR-376a sequence. [score:1]
To avoid the influence of endogenous rno-miR-376a, we used HEK293 cells rather than rat granulosa cells (Fig. 6). [score:1]
Next, we investigated the effects of rno-miR-144, rno-miR-376a, and rno-miR-451 on GRP78 mRNA expression in granulosa cells isolated from DES -treated immature rats (Fig. 2). [score:1]
Rat GRP78 mRNA (A), rno-miR-144 (B), rno-miR-376a (C), and rno-miR-451 (D) expression levels were measured using real-time RT-PCR as described in the. [score:1]
The amounts of GRP78 mRNA, rno-miR-144, rno-miR-376a, and rno-miR-451 in the hCG 0 h group were set at 1. Data were normalized for 18S rRNA (for GRP78 mRNA) and 4.5S RNA(H) (for rno-miR-144, rno-miR-376a, and rno-miR-451) levels in each sample and represent the mean ±SE of 3 independent experiments. [score:1]
Furthermore, miR-376a did not show a substantial change in the absence of hCG treatment (Fig. 3), confirming that hCG has an important role for the induction of miR-376a. [score:1]
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5
[+] score: 48
When compared with expression profiles of miRNAs associated with renal cancer, there was a 15% overlap with the miRNAs described in a recent report [54]; however, only miR-376a [67] out of the highly upregulated miRNAs, and miR-638, miR-200b and miR-200c from the highly downregulated miRNAs, were found to be in common between our studies and other studies [67], [70], [71], [72]. [score:8]
The double-stranded oligonucleotides encoding the pre-miRNA sequences of miR-376a, miR-299, miR-382 or irrelevant miRNA (a miR -negative control, predicted not to target any known vertebrate gene) were cloned into the pcDNA6.2-GW/EmGFP-miR expression vector such that the pre-miRNA insertion site was in the 3′ untranslated (3′UTR) region of the green fluorescent protein (GFP) gene as per the instruction manual (Invitrogen, Carlsbad, CA). [score:7]
0014416.g004 Figure 4 (A) of stably expressing miR-376a, miR376abc (a polycistronic cluster of miR-376a, miR-376b and miR-376c), miR-299-5p or miR -negative and 10-87 LP cells; (B) with stably expressing miR-376a, miR-376abc, miR-299-5p or miR -negative 10-87 HP cells. [score:5]
Indeed, the overexpression of miR-376a and the polycistronic cluster of miR-376a, miR-376b and miR-376c in non-invasive 10-87 LP cells were able to recapitulate the migration and invasion phenotypes of 10-87 HP cells. [score:3]
A human cytomegalovirus (HCMV) miRNA acts synergistically with a cellular miR-376a to suppress one of the major histocompatibility complex class I polypeptide-related sequences (MICB) during HCMV infection [47]. [score:3]
Recently, a target and function of miR-376a has been identified. [score:3]
We have identified miR-376a and the polycistronic miR-376abc as having a functional role in establishing the enhanced cell migration and cell invasion phenotypes, which are correlated with the expression of the VERO cell tumorigenic phenotype. [score:3]
To determine whether the overexpression of the identified signature miRNAs could confer phenotypic changes, stable cell lines were created by cloning the pre-miRNA sequences of miR-376a, miR-376abc, miR-299, or miR-382 into the pcDNA6.2-GW/EmGFP-miR vector, which contains a green fluorescent protein (GFP) cassette, and introducing them into the non-tumorigenic 10-87 LP cells. [score:3]
As found for 10-87 HP cells and 10-87 T cells, SF-VERO cells and A4497 VERO cells expressed increased levels of miR-376a, miR-654-3p, miR-543, and miR-382 over the levels found in pAGMK cells (Table 4). [score:3]
An expression plasmid for the polycistronic gene cluster for miR-376a, miR-376b and miR-376c was generated by amplifying 200 bp up-stream and 200 bp down-stream of the genes (termed as miR-376abc) in VERO cell DNA using primers 5′-CCCTCGACGAGAGTGATGGAAGGTGAATC-3′ and 5′-CCAGATCTATACTGAGAACACAGCCTTGT-3′. [score:2]
In agreement with the wound-healing assay, over -expression of miR-376a or miR-376abc also resulted in more than a four-fold increase in invasiveness, whereas miR-299 or miR-382 had no effect (Fig. 4B). [score:2]
The cells expressing miR-376a or miR-376abc displayed an increase in migration compared with control 10-87 LP cells. [score:2]
The following oligonucleotides were used to generate the pre-miRNAs: miR-376a sense, 5′-tgctGTAAAAGGTAGATTCTCCTTCTATGAGTACATTATTTATGATTAATCATAGAGGAAAATCCACGTTTTC-3′ and miR-376a anti-sense 5′- cctgGAAAACGTGGATTTTCCTCTATGATTAATCATAAATAATGTACTCATAGAAGGAGAATCTACCTTTTAC-3′. [score:1]
While the specific effect of miR-376a on tumorigenicity has not yet been demonstrated, it is plausible to suggest that the 10-87 VERO cells might use a similar mechanism as does HCMV to escape the immune system during tumor growth in athymic nude mice. [score:1]
These experiments demonstrated that miR-376a and miR-376abc were sufficient to confer the cell migration and invasion phenotype. [score:1]
qRT-PCR analysis confirmed that miR-376a, miR-654-3p, miR-543, miR-382, miR-31, miR-200c, miR-218, and miR-183 paralleled the microarray miRNA levels. [score:1]
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6
[+] score: 41
Figure 4. The ‘extended VCR’ of stratum 2 (shared by Homo and Pelodiscus sequences): (a) miR-16 target site (also shown in Fig. 2e) and nearby target sites for miR-376a, miR-335-3p, miR-493 and miR-379 (the Xenopus sequence contains a 44-bp insertion at the site of the asterisk that includes two target sites for miR-335-3p are shown in red); (b) conserved pair of target sites for miR-320a and miR-182; (c) conserved triplet of target sites for miR-378, miR-99a and miR-30a A notable feature of stratum 2 is a pair of complementary sequences, 800 nucleotides apart, that are predicted to form the stems of a strong double helix (18 bp, –32.3 kcal/mol). [score:11]
Figure 4. The ‘extended VCR’ of stratum 2 (shared by Homo and Pelodiscus sequences): (a) miR-16 target site (also shown in Fig. 2e) and nearby target sites for miR-376a, miR-335-3p, miR-493 and miR-379 (the Xenopus sequence contains a 44-bp insertion at the site of the asterisk that includes two target sites for miR-335-3p are shown in red); (b) conserved pair of target sites for miR-320a and miR-182; (c) conserved triplet of target sites for miR-378, miR-99a and miR-30aA notable feature of stratum 2 is a pair of complementary sequences, 800 nucleotides apart, that are predicted to form the stems of a strong double helix (18 bp, –32.3 kcal/mol). [score:11]
Either the miR-675 and miR-376 binding sites were targets for unidentified ancient microRNAs, perhaps still present in Pelodiscus and Callorhinchus, or the more recent imprinted microRNAs evolved to target sequences that were conserved for functions unrelated to binding by microRNAs. [score:5]
If the latter scenario is correct, then the VCR is likely to have been an original target of miR-675 and miR-376 which evolved to target its sequence. [score:5]
It is notable that miR-675 and miR-376 are both imprinted and maternally expressed [12, 27]. [score:3]
miR-376a, miR-379 and miR-493 are encoded in a large cluster of maternally expressed imprinted microRNAs found only in eutherian mammals [27]. [score:3]
This ‘extended VCR’ contains a remarkable concentration of predicted binding sites for microRNAs, including miR-335-3p [38], miR-376a [26] and miR-493 [39]. [score:1]
The miR-376 binding site occurs distal to the end of the short transcript. [score:1]
By contrast, miR-675 is known only from marsupial and eutherian mammals [35, 36] and miR-376 only from eutherian mammals [27]. [score:1]
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7
[+] score: 27
Most interestingly, 3 of these resistance-relevant miRNA candidates showed a similar pattern of deregulation in both tumour types: miR-141 and miR-200b were significanty upregulated whereas miR-376a was significantly downregulated (see Table  1 and Figure  6). [score:8]
Specifically, PPI treatment led to upregulation of miR-141 and miR-200b and downregulaton of miR-376a in SCC and EAC cells. [score:7]
Specifically, miR-141 and miR-200b were upregulated, whereas miR-376a was downregulated after PPI treatment in both tumour types. [score:7]
In prostate cancer cells, miR-376 was shown to be involved in regulation of proliferation, apoptosis, migration and cell invasion [43]. [score:2]
Most interestingly, we found three miRNAs (namely miR-141, miR-200b and miR-376a) to be deregulated in a similar fashion in both tumour subtypes, implying that these miRNAs might in general be affected by PPI treatment. [score:2]
Namely, we selected miR-16, miR-21, miR-23a, miR-24, miR-26a, miR-106, miR-141, miR-155, miR-196a, miR-200a, miR-200b, miR-200c, miR-221, miR-222, miR-296-5p, miR-376a, miR-429 and let-7i for this study. [score:1]
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8
[+] score: 25
Of a number of upregulated miRNAs, miRNA-376a, miR-127, miR-34a, miR-300, miR-342-3p were downregulated following metformin treatment in MCD-fed mice. [score:7]
The five downregulated miRNAs i. e., miRNA-376a, miRNA-127, miRNA-34a, miRNA-300 and miRNA-342-3p, were identical to five of the 71 upregulated miRNAs in control and MCD-fed mice. [score:7]
Notably, miR-122, miR-194, miRNA-101b, and miRNA-705 were upregulated and miRNA-376a, miRNA-127, miRNA-34a, miRNA-300 and miRNA-342-3p were downregulated in the liver tissue of MCD-fed mice treated with or without metformin (Table IB and Fig. 6). [score:7]
Recently, miR-376a downregulation has been shown to be associated with arsenic trioxide (ATO) -induced apoptosis in human retinoblastoma cells (16). [score:4]
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9
[+] score: 20
Thus miR-98, miR-323-3p, miR-330-3p, miR-376a, miR-494, miR-598 were down-regulated by UVA and UVB, while miR-191, miR-376c and miR-501-5p were up-regulated by both. [score:7]
Among the 6 down-regulated miRNAs after UVA- and UVB-irradiation (miR-98, miR-323-3p, miR-330-3p, miR-376a, miR-494, miR-598) 3 miRNAs (miR-98, miR-330-3p and miR-376a) shared the common regulator element Hox-2.3-undefined-site-2 (gggggtgggggggag) in their promoter regions. [score:5]
Interestingly, of these ten commonly regulated microRNAs miR-98, miR-191, miR-323-3p, miR-330-3p, miR-494, and miR-598 were reported to be also deregulated after ionizing radiation [29], [30], [31] and miR-376a was shown to be a regulator of apoptosis in response to arsenic trioxide treatment [32]. [score:4]
The down-regulated miRNA-set consists of miR-98, miR-323-3p, miR-330-3p, miR-376a, miR-494 and miR-598. [score:4]
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10
[+] score: 16
Kawahara and colleagues demonstrated that A-to-I editing of pri-miR-376 results in the redirection of its silencing effects to a different set of target mRNAs. [score:4]
Overall, these data indicate the essential role of ADAR2 editing in glioblastoma, acting on multiple targets (CDC14B, pri-miR-221/222, pri-miR-21, miR-376a-5p, GRIA2) that together contribute to varying extents to cancer progression. [score:3]
The miR-376 is edited by ADAR2 within its “seed” sequence (+4 site), an essential region for RNA duplex formation with the complementary target mRNA [95]. [score:3]
High-grade gliomas accumulate the unedited form of miR-376a-5p, which promotes cell migration and invasion while edited miR-376a-5p suppresses these features [140]. [score:3]
1 (Spi1) ADAR1[132] Glioblastoma (GBM) CDC14B ADAR2[135] pri-miR-221/222 ADAR2[139] Pri-miR-21 ADAR2[139] miR-376a-5p ADAR2[140] GRIA2 ADAR2[141] Aicardi-Goutiéres Syndrome (AGS) ? [score:1]
Choudhury Y. Tay F. C. Lam D. H. Sandanaraj E. Tang C. Ang B. T. Wang S. Attenuated adenosine-to-inosine editing of microRNA-376a* promotes invasiveness of glioblastoma cells J. Clin. [score:1]
Decrease of ADAR2 activity in glioblastoma can also affects miR-376a-5p activity. [score:1]
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11
[+] score: 16
Other miRNAs from this paper: hsa-mir-376c, hsa-mir-376a-1, hsa-mir-376b
Thus, PRPS1 expression plays a role in fetal inner ear development, and mutations to the PRPS1 gene or to miRNA-376 may result in abnormal organ development. [score:6]
In adult inner ear, the expression of miR-376a-3p/b-3p is restricted within ganglion neurons of auditory and vestibular systems as well as the cells in the stria vascularis [8]. [score:3]
Our previous study demonstrated that miR-376a-3p, b-3p, c-3p are present in mouse embryonic inner ears and intensive expression of miR-376a-3p/b-3p was detected in the sensory epithelia and ganglia of both auditory and vestibular portions of the inner ear [8]. [score:3]
The transcript levels of PRPS1 are regulated by mir-376. [score:2]
PRPS1, transcriptionally regulated by microRNA-376 [5], codes for PRS-I, which catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) from adenosine triphosphate (ATP) and ribose-5-phophate (R5P) [4, 6]. [score:2]
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12
[+] score: 15
, High Wycombe, UK) analysis of 1733 human microRNAs and validation by qRT-PCR showed microRNA-21, microRNA-99a, microRNA-100, microRNA-125b, microRNA-138, microRNA-147b, microRNA-148a, microRNA-210, microRNA-376a, and microRNA-455-3p to be significantly upregulated, whereas microRNA-31-star, microRNA-330-3p, microRNA-330-5p, microRNA-378d, microRNA-422a, and microRNA-486-5p were significantly downregulated. [score:7]
p < 0.05 indicates significance Expression of in vitro dysregulated microRNA-376a, microRNA-330-3p, microRNA-330-5p, microRNA-378d, microRNA-422a, microRNA-455-3p, and microRNA-486-5p did not differ between PDAC and control. [score:4]
p < 0.05 indicates significance Expression of in vitro dysregulated microRNA-376a, microRNA-330-3p, microRNA-330-5p, microRNA-378d, microRNA-422a, microRNA-455-3p, and microRNA-486-5p did not differ between PDAC and control. [score:4]
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13
[+] score: 14
Importantly, in the case of mir-376a-5p, mir-376b-5p, mir-376a-3p and mir-376-3p the edited nucleoside resides in the seed region, which is instrumental in targeting the miRNA to its target and could therefore lead to an altered target spectrum. [score:7]
The most abundantly edited miRNA is mir-376b, in the brain (Figure 2B), fitting with the observation that in murine and human brains, mir-376a/b/c are targets of the RNA editing machinery [51, 52]. [score:3]
Furthermore, we confirmed specific A to I editing in brain for mir-376a/b/c and identified mir-377 as a novel editing target. [score:3]
We find the mir-376a/c isoforms to be edited as well, albeit to a lesser extent (Figure 2B). [score:1]
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14
[+] score: 14
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19a, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-23a, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-96, hsa-mir-99a, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-192, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-139, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-210, hsa-mir-181a-1, hsa-mir-214, hsa-mir-215, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-140, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-134, hsa-mir-136, hsa-mir-146a, hsa-mir-150, hsa-mir-185, hsa-mir-190a, hsa-mir-194-1, hsa-mir-195, hsa-mir-206, hsa-mir-200c, hsa-mir-155, hsa-mir-181b-2, hsa-mir-128-2, hsa-mir-194-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-99b, hsa-mir-296, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-370, hsa-mir-373, hsa-mir-374a, hsa-mir-375, hsa-mir-376a-1, hsa-mir-151a, hsa-mir-148b, hsa-mir-331, hsa-mir-338, hsa-mir-335, hsa-mir-423, hsa-mir-18b, hsa-mir-20b, hsa-mir-429, hsa-mir-491, hsa-mir-146b, hsa-mir-193b, hsa-mir-181d, hsa-mir-517a, hsa-mir-500a, hsa-mir-92b, hsa-mir-33b, hsa-mir-637, hsa-mir-151b, hsa-mir-298, hsa-mir-190b, hsa-mir-374b, hsa-mir-500b, hsa-mir-374c, hsa-mir-219b, hsa-mir-203b
In a review, Gramantieri et al. (2008) show miRNAs aberrantly expressed in HCC compared to non-tumorous liver tissue (up -expression of miR-33, miR-130, miR-135a, miR-210, miR-213, miR-222, miR-331, miR-373, miR-376a, and down -expression of miR-130a, miR-132, miR-136, miR-139, miR-143, miR-145, miR-150, miR-200a, miR-200b, miR-214). [score:6]
Stimulation of HCC proliferationBudhu et al., 2008; Gramantieri et al., 2008; Huang et al., 2009, 2011 miR-373 Invasion and metastasisMeng et al., 2007; Bartels and Tsongalis, 2009; Wu et al., 2011 miR-374 DevelopmentWang et al., 2008; Wong et al., 2008, 2010; Koh et al., 2013 miR-375 Stimulation of HCC proliferationLiu et al., 2010; He et al., 2012 miR-376a Proliferation and apoptosisMeng et al., 2007; Zheng et al., 2012b miR-423 Enhanced CDK2 activityLin et al., 2011 miR-491-5p Inhibition of TNF-α-related apoptosisYoon et al., 2010 miR-500 Elevated in HCC, returned to physiologic level after surgical interventionYamamoto et al., 2009 miR-637 Active STAT3Zhang et al., 2011 let-7a/a-1/a-2/b/c/d/e/f/f-2/g Development. [score:5]
miR-376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma. [score:3]
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15
[+] score: 11
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-96, mmu-let-7g, mmu-let-7i, mmu-mir-124-3, mmu-mir-9-2, mmu-mir-141, mmu-mir-152, mmu-mir-182, mmu-mir-183, mmu-mir-199a-1, hsa-mir-199a-1, mmu-mir-200b, mmu-mir-205, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-182, hsa-mir-183, hsa-mir-199a-2, hsa-mir-199b, hsa-mir-205, hsa-mir-214, hsa-mir-200b, mmu-let-7d, mmu-mir-130b, hsa-let-7g, hsa-let-7i, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-141, hsa-mir-152, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, mmu-mir-200a, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-96, hsa-mir-200c, mmu-mir-200c, mmu-mir-214, mmu-mir-199a-2, mmu-mir-199b, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-200a, hsa-mir-130b, hsa-mir-376a-1, mmu-mir-376a, dre-mir-7b, dre-mir-7a-1, dre-mir-7a-2, dre-mir-182, dre-mir-183, dre-mir-199-1, dre-mir-199-2, dre-mir-199-3, dre-mir-205, dre-mir-214, hsa-mir-429, mmu-mir-429, hsa-mir-450a-1, mmu-mir-450a-1, dre-mir-429a, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-7a-3, dre-mir-9-1, dre-mir-9-2, dre-mir-9-4, dre-mir-9-3, dre-mir-9-5, dre-mir-9-6, dre-mir-9-7, dre-mir-96, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-130b, dre-mir-141, dre-mir-152, dre-mir-200a, dre-mir-200b, dre-mir-200c, hsa-mir-450a-2, dre-let-7j, mmu-mir-450a-2, dre-mir-429b, mmu-let-7j, mmu-let-7k, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
We found eight miRs differentially expressed, six down-regulated (miR-9, miR-141, miR-200a, miR-200b, miR-429 and miR-376a) and two up-regulated (miR-450a-5p and miR130b*) in the Dlx5 [−/−] OE (Fig.  1a). [score:9]
No Dlx5 binding site was predicted within a 50 kb range from the miR-9.1, miR-141, miR-200c and miR-376a loci. [score:1]
The miR-200a, - 200b and - 429 loci are closely located on chromosome 4, while miR-141 and -200c are closely located on chromosome 6. miR-376a is clustered with 16 other miRs on chromosome 12. [score:1]
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16
[+] score: 11
Among these, hsa-miR-376a-5p and hsa-miR-221-5p were regulated by translation regulator-related mRNA, EIF2C2, while hsa-miR-377-5p directly regulated by DICER1. [score:7]
Hsa-mir-376a-5p has been known to suppress proliferation while inducing apoptosis in hepatocellular carcinoma cells 37. [score:3]
The miRNAs are namely hsa-miR-7-5p, hsa-miR-221-5p, hsa-miR-377-5p, hsa-miR-376a-5p, and let-7f-2-3p. [score:1]
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17
[+] score: 10
We already showed that two miRNAs from this cluster, miR-376a and miR-367c, which are significantly down-regulated in melanoma, target the insulin-growth-factor-1 receptor and can decrease the malignant phenotype of melanoma cells upon ectopic expression [15]. [score:8]
Formosa A, Markert EK, Lena AM, Italiano D, Finazzi-Agro E, Levine AJ, et al. s, miR-154, miR-299-5p, miR-376a, miR-376c, miR-377, miR-381, miR-487b, miR-485-3p, miR-495 and miR-654-3p, mapped to the 14q32.31 locus, regulate proliferation, apoptosis, migration and invasion in metastatic prostate cancer cells. [score:2]
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[+] score: 10
miR-374 was also downregulated in older participants in an earlier study [18], but in contrast with our study, miR-376 was upregulated in older participants in another report [20]. [score:7]
Interestingly, none of the six miRNAs has previously been shown to play a mechanistic role in aging, and none has been implicated in heart disease, but many have been shown to function and/or act as biomarkers in different cancers (miR-211: melanoma cell invasive-ness; head, neck, renal cell carcinomas; pancreatic cancer; miR-374: small cell lung cancer; miR-340: osteosarcoma, colorectal cancer, breast cancer, gastric cancer; miR-376: glioblastoma, hepato-cellular carcino-ma) [24]. [score:3]
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[+] score: 9
Overall, 31% and 50% of the miR-376c and 86% and 50% of the miR-376a were expressed as the edited form in HCC and ANL, respectively. [score:3]
A recent study has reported tissue-specific editing of miR-376 cluster members and the expression of edited mature miR-376 RNAs in certain tissues [20]. [score:3]
For miR-376c, miR-376a, miR-34a, miR-503, miR-21, and miR-122, the RNA modifications were detected using both methods, and the possibility of a single nucleotide polymorphism at any of the RNA editing sites was excluded by comparison with the public database OncoDb HCC. [score:1]
First, in miR-376c and miR-376a, members of miR-376 cluster, specific adenosine (A) residues in the seed sequence (+6 site) were detected as guanosine (G) in the sequencing chromatogram, which suggests adenosine to inosine (I) editing [20]. [score:1]
Modified miR-376c, miR-376a, miR-34b*, and miR-503 are detected by RT-PCR and conventional cloning. [score:1]
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[+] score: 9
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-17, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-27a, hsa-mir-30a, hsa-mir-93, hsa-mir-96, hsa-mir-99a, hsa-mir-100, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-105-1, hsa-mir-105-2, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-10a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-205, hsa-mir-212, hsa-mir-181a-1, hsa-mir-222, hsa-mir-224, hsa-let-7g, hsa-let-7i, hsa-mir-23b, hsa-mir-27b, hsa-mir-30b, hsa-mir-122, hsa-mir-125b-1, hsa-mir-132, hsa-mir-141, hsa-mir-145, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-146a, hsa-mir-150, hsa-mir-184, hsa-mir-188, hsa-mir-320a, hsa-mir-181b-2, hsa-mir-30c-1, hsa-mir-302a, hsa-mir-34c, hsa-mir-30e, hsa-mir-302b, hsa-mir-302c, hsa-mir-302d, hsa-mir-371a, hsa-mir-372, hsa-mir-376a-1, hsa-mir-378a, hsa-mir-383, hsa-mir-339, hsa-mir-133b, hsa-mir-345, hsa-mir-425, hsa-mir-483, hsa-mir-146b, hsa-mir-202, hsa-mir-193b, hsa-mir-181d, hsa-mir-498, hsa-mir-518f, hsa-mir-518b, hsa-mir-520c, hsa-mir-518c, hsa-mir-518e, hsa-mir-518a-1, hsa-mir-518d, hsa-mir-518a-2, hsa-mir-503, hsa-mir-513a-1, hsa-mir-513a-2, hsa-mir-548a-1, hsa-mir-548b, hsa-mir-548a-2, hsa-mir-548a-3, hsa-mir-548c, hsa-mir-645, hsa-mir-548d-1, hsa-mir-548d-2, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-744, hsa-mir-548e, hsa-mir-548j, hsa-mir-548k, hsa-mir-548l, hsa-mir-548f-1, hsa-mir-548f-2, hsa-mir-548f-3, hsa-mir-548f-4, hsa-mir-548f-5, hsa-mir-548g, hsa-mir-548n, hsa-mir-548m, hsa-mir-548o, hsa-mir-548h-1, hsa-mir-548h-2, hsa-mir-548h-3, hsa-mir-548h-4, hsa-mir-302e, hsa-mir-302f, hsa-mir-548p, hsa-mir-548i-1, hsa-mir-548i-2, hsa-mir-548i-3, hsa-mir-548i-4, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-548q, hsa-mir-548s, hsa-mir-378b, hsa-mir-548t, hsa-mir-548u, hsa-mir-548v, hsa-mir-548w, hsa-mir-320e, hsa-mir-548x, hsa-mir-378c, hsa-mir-548y, hsa-mir-548z, hsa-mir-548aa-1, hsa-mir-548aa-2, hsa-mir-548o-2, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-548h-5, hsa-mir-548ab, hsa-mir-378f, hsa-mir-378g, hsa-mir-548ac, hsa-mir-548ad, hsa-mir-548ae-1, hsa-mir-548ae-2, hsa-mir-548ag-1, hsa-mir-548ag-2, hsa-mir-548ah, hsa-mir-378h, hsa-mir-548ai, hsa-mir-548aj-1, hsa-mir-548aj-2, hsa-mir-548x-2, hsa-mir-548ak, hsa-mir-548al, hsa-mir-378i, hsa-mir-548am, hsa-mir-548an, hsa-mir-371b, hsa-mir-548ao, hsa-mir-548ap, hsa-mir-548aq, hsa-mir-548ar, hsa-mir-548as, hsa-mir-548at, hsa-mir-548au, hsa-mir-548av, hsa-mir-548aw, hsa-mir-548ax, hsa-mir-378j, hsa-mir-548ay, hsa-mir-548az, hsa-mir-548ba, hsa-mir-548bb, hsa-mir-548bc
MiR-376a negatively correlated with PCNA mRNA expression in fetal and neonatal mouse ovaries and directly bound to PCNA untranslated region [30], while there is no data available for humans at present. [score:5]
The data derived from the mouse mo del show that miRNA-376a regulates the primordial follicle assembly in the ovary by modulating the expression of proliferating cell nuclear antigen (PCNA) gene in mouse fetal and neonatal ovaries. [score:4]
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[+] score: 9
Unedited mir-376a* promotes the migration and invasion of glioma cells, whereas edited mir-376a* suppresses these features. [score:3]
However, in rare cases, such as mir-376, RNA editing causes base substitution in the seed sequence and generates edited mature miRNAs with unique target genes and functions different from those of the unedited miRNAs (Kawahara et al., 2007). [score:3]
These results suggest that the attenuation of A-to-I editing of mir-376a* promotes the invasiveness of glioblastoma. [score:1]
Recently, the efficiency of A-to-I editing of mir-376a* was found to be significantly attenuated in glioblastoma cells (Choudhury et al., 2012). [score:1]
Attenuated adenosine-to-inosine editing of microRNA-376a* promotes invasiveness of glioblastoma cells. [score:1]
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22
[+] score: 8
F: qRT-PCR analysis was performed to assess the expression of miR-106a (i) and miR-376a (ii) in HCC cells treated with cisplatin. [score:3]
B and C: qRT-PCR analysis was performed to assess the expression of miR-376a and miR-122a in HCC cells treated with 5-fluorouracil (B) and pirarubicin (C). [score:3]
Importantly, miR-376a-P85α and miR-122a-Bcl-w[29- 30], which have been validated as deregulated axes in HCC cells, were modified after 5-fluorouracil and pirarubicin treatment, as shown by using qRT-PCR (Figure. [score:2]
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[+] score: 8
Other miRNAs from this paper: hsa-mir-127, hsa-mir-136, hsa-mir-376c, hsa-mir-376a-1, hsa-mir-377
While expression of miR-136, miR-376a and miR-377 did not significantly change during treatment, expression of miR-376c and miR-127-3p was significantly increased by Aza treatment and was further elevated by the combined treatment with Aza and PBA. [score:5]
At least eight microRNAs within this cluster have been identified as potential tumor suppressors, among them mir-376a and miR-377, silenced in GCT [9, 11]. [score:3]
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[+] score: 7
Recent studies indicate that during human pancreatic development miR-7, miR-9, miR-375 and miR-376 are specific islet microRNAs expressed at high levels [18, 19]. [score:4]
Please note that even though in some cases the group III colorgram suggests a change of expression throughout the gestational stages (e. g miR-376, miR-378, etc), these were found to be not statistically significant. [score:3]
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[+] score: 7
These included predicted binding of spliced genes to three forms of hsa-miR-376 (a–c forms), hsa-mir-544 targeted at the same spliced gene (ITGAL) and the inflammation-related hsa-mir-150 [87] predicted to target the disease spliced gene FGD4. [score:7]
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26
[+] score: 7
As a result, we selected 11 miRNAs (miR-27a, miR-27b, miR-145, miR-185, miR-197, miR-203, miR-221, miR-222, miR-338-3p, miR-376a, and miR-376b) that were potentially regulated by CD82 to target FZD2, -3, -5, -7, and -9 for further study (Table 1). [score:4]
No significant differences in miR-27a, miR-27b, miR-145, miR-185, miR-197, miR-221, miR-222, miR-376a, or miR-376b expression levels were observed between h1299/zeo and h1299/CD82 cells (Fig 1). [score:3]
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[+] score: 7
The comparison between control- and MPA -treated cells revealed that 16 miRNAs were significantly modulated by more than two-fold (P < 0.05, Figure 1A), nine miRNAs were upregulated (miR-191*, miR-17*, miR- 470*, miR-451, miR-702, miR-434-3p, miR-493, miR-23a* and miR-485*) and seven were downregulated (miR-378*, miR-376a, miR-224, miR-190b, miR-16, miR-410 and miR-197) (Figure 1B). [score:7]
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[+] score: 7
Since possible target genes have been identified for only a few imprinted microRNAs, e. g. miR-134, miR-376a, miR-370, and the microRNAs embedded in the antisense transcript of the Retrotransposon-like 1 (Rtl1) gene [19, 22, 29- 32], we established a pipeline that combines different algorithms to predict microRNA target genes computationally. [score:5]
For example, the sequences with the highest overlap of 26.2%/48.8% (hsa-miR-376a and hsa-miR-376b) differ in only two bases (one in length and one base substitution). [score:1]
The murine sequence mmu-miR-376a is one nucleotide shorter and is aligned with two instead of three mismatches. [score:1]
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[+] score: 7
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-18a, hsa-mir-19a, hsa-mir-19b-1, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-25, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-31, hsa-mir-33a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-96, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-103a-2, hsa-mir-103a-1, hsa-mir-107, hsa-mir-16-2, hsa-mir-196a-1, hsa-mir-198, hsa-mir-129-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-196a-2, hsa-mir-199b, hsa-mir-203a, hsa-mir-204, hsa-mir-210, hsa-mir-211, hsa-mir-212, hsa-mir-181a-1, hsa-mir-214, hsa-mir-215, hsa-mir-216a, hsa-mir-217, hsa-mir-219a-1, hsa-mir-221, hsa-mir-222, hsa-mir-223, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-1-2, hsa-mir-15b, hsa-mir-23b, hsa-mir-30b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-130a, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-137, hsa-mir-138-2, hsa-mir-140, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-127, hsa-mir-129-2, hsa-mir-138-1, hsa-mir-146a, hsa-mir-150, hsa-mir-184, hsa-mir-185, hsa-mir-195, hsa-mir-206, hsa-mir-320a, hsa-mir-200c, hsa-mir-1-1, hsa-mir-155, hsa-mir-181b-2, hsa-mir-128-2, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-200a, hsa-mir-101-2, hsa-mir-219a-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-99b, hsa-mir-296, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-365a, hsa-mir-365b, hsa-mir-375, hsa-mir-376a-1, hsa-mir-378a, hsa-mir-382, hsa-mir-383, hsa-mir-151a, hsa-mir-148b, hsa-mir-338, hsa-mir-133b, hsa-mir-325, hsa-mir-196b, hsa-mir-424, hsa-mir-20b, hsa-mir-429, hsa-mir-451a, hsa-mir-409, hsa-mir-412, hsa-mir-376b, hsa-mir-483, hsa-mir-146b, hsa-mir-202, hsa-mir-181d, hsa-mir-499a, hsa-mir-92b, hsa-mir-33b, hsa-mir-151b, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-301b, hsa-mir-216b, hsa-mir-103b-1, hsa-mir-103b-2, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-378b, hsa-mir-320e, hsa-mir-378c, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-219b, hsa-mir-203b, hsa-mir-451b, hsa-mir-499b, hsa-mir-378j
The edited miR-376a was expressed in specific tissues, and it regulated target genes different than the unedited miR-376a (Kawahara et al. 2007). [score:6]
For instance, A-to-I editing inside the seed sequence has been observed in some miRNAs, such as miR-151, miR-376a, miR-376b, and miR-368 (Kawahara et al. 2007; García-López et al. 2013). [score:1]
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[+] score: 7
For the three miRNAs that are edited in the 5' seed region (miR-151, miR-376a and miR-379), comparison of over-represented GO terms associated with the predicted targets of edited and unedited copies reveals distinct differences (Figure 3). [score:3]
For the three miRNAs in which the edited adenosine is at a position two to seven bases from the 5' end of the miRNA (miR-151, miR376a and miR-379) over half of the targets of the edited miRNA are unique to the edited miRNA. [score:3]
miR-376a and antisense miR-451 were each edited at two sites, and antisense miR-371 was edited at four sites. [score:1]
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31
[+] score: 6
Biological support to this mode was given by Nachmani et al. [14] showing that hcmv-miR-UL112-1 and hsa-miR-376, which have distinct target sites on MICB mRNA, cooperate within infected cells to down-regulate MICB. [score:6]
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[+] score: 6
Importantly, the miRNAs miR-495-3p, miR-654-3p, miR-376a-3p and miR-487b-3p exhibited marked downregulation after 5 weeks in contrast to a slight reduction of expression observed for most miRNA genes from this region. [score:6]
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33
[+] score: 6
A single A to I conversion in the seed of miR-376a-5p, for example, redirects the edited miRNA to a new set of mRNA targets [25]. [score:4]
Congruent with previous studies, A to G changes occurred in >60% of the reads for members of the miR-376 family (miR-376a, b, and c) at nucleotide position six of the mature miRNA sequence (Table 1, Fig. S3A) [36]. [score:1]
Furthermore, several of these miRNA variants (miR-376 family members, miR-411, miR-379, and miR-320a) have previously been described in deep sequencing studies performed on human brain [36], [37], and therefore, are not specific to glioblastoma. [score:1]
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[+] score: 6
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-21, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-27a, hsa-mir-29a, hsa-mir-30a, hsa-mir-98, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-107, hsa-mir-16-2, hsa-mir-198, hsa-mir-148a, hsa-mir-30d, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-205, hsa-mir-210, hsa-mir-181a-1, hsa-mir-222, hsa-mir-224, hsa-mir-200b, hsa-let-7g, hsa-let-7i, hsa-mir-23b, hsa-mir-27b, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-128-1, hsa-mir-132, hsa-mir-137, hsa-mir-140, hsa-mir-141, hsa-mir-142, hsa-mir-143, hsa-mir-144, hsa-mir-153-1, hsa-mir-153-2, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-125b-2, hsa-mir-126, hsa-mir-134, hsa-mir-136, hsa-mir-146a, hsa-mir-150, hsa-mir-184, hsa-mir-185, hsa-mir-186, hsa-mir-206, hsa-mir-320a, hsa-mir-200c, hsa-mir-128-2, hsa-mir-200a, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-299, hsa-mir-26a-2, hsa-mir-373, hsa-mir-376a-1, hsa-mir-342, hsa-mir-133b, hsa-mir-424, hsa-mir-429, hsa-mir-433, hsa-mir-451a, hsa-mir-146b, hsa-mir-494, hsa-mir-193b, hsa-mir-455, hsa-mir-33b, hsa-mir-644a, hsa-mir-548d-1, hsa-mir-548d-2, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-301b, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, hsa-mir-320e, hsa-mir-3613, hsa-mir-4668, hsa-mir-4674, hsa-mir-6722
It is demonstrated that during preclinical stage of prion disease, miRNAs abundant in synaptoneurosomes including miRNA-124a-3p, miRNA-136-5p and miRNA-376a-3p are increased. [score:3]
Boese et al. (2016) recently demonstrated that during preclinical stage of prion disease, miRNAs enriched in synaptoneurosomes including miRNA-124a-3p, miRNA-136-5p and miRNA-376a-3p were elevated. [score:3]
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35
[+] score: 6
The canonical version of miR-376 and its seed-altered isomiR were shown to have highly distinct target sets [29], highlighting the biological importance of 5′-isomiRs. [score:3]
Perhaps the best-studied example of this phenomenon is the A-to-I editing of the miR-376 primary transcript leading to the expression of a 5′-isomiR of miR-376 with a modified seed [29]. [score:3]
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36
[+] score: 6
Modified seed sequences were observed in pri-miR-376a [115], for instance, resulting in a change in the target mRNA. [score:3]
While only ADAR2 is responsible for editing pri-miR-376a, one could speculate similar mechanisms in ADAR1′s pri-miRNA targets as well. [score:3]
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37
[+] score: 6
Three miRNAs (hsa-miR-193a-3p, hsa-miR-34a, hsa-miR-376a) upregulated in PB ECFC-derived cells from all donors tested were chosen for validation by real time q-RT-PCR based on preliminary screen of anti-proliferative activity using mimics. [score:4]
As illustrated in Fig. 1D, for hsa-miR-193a-3p, hsa-miR-34a, hsa-miR-376a, CB ECFC-derived cells showed reduced expression of these miRNAs (0.50 ± 0.03; 0.51 ± 0.02 and 0.39 ± 0.004 fold respectively; p < 0.01, one-way ANOVA) compared to PB ECFC-derived cells (normalized to 1). [score:2]
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38
[+] score: 6
o.   fold changep-valuehsa-miR-654-5p3.880.00014hsa-miR-493*3.100.00016hsa-miR-4102.930.00029hsa-miR-376a*2.660.00072hsa-miR-7582.870.00073hsa-miR-3812.390.00094hsa-miR-5432.070.00119hsa-miR-5393.060.00124hsa-miR-487b2.020.00186hsa-miR-337-5p2.540.00195hsa-miR-136*2.790.00246hsa-miR-154*2.270.00337hsa-miR-330-3p2.440.00759 hsa-miR-421 2.45 0.01282We also identified miRNAs with expression levels that varied according to gender and age. [score:3]
In regards to age, we discovered that the expression levels of 14 miRNAs (miR-654-5p, miR-493*, miR-410, miR-376a*, miR-758, miR-381, miR-543, miR-539, miR-487b, miR-337-5p, miR-136*, miR-154*, miR-330-3p, and miR-421) were significantly higher in HCC up to 66 years old than in HCC over 67 years old. [score:3]
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39
[+] score: 5
For example, lncRNA MALAT1 may promote OS cell growth through inhibition of miR-376A, leading to increased expression of TGFA [10]. [score:5]
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40
[+] score: 5
A signature of 5 miRNAs (miR-376a, miR-381, miR-411, miR-432, and miR-487) along with miR-203 that can be mapped to both chromosome 14q32.1 and 14q32.33 is shown in ependymoma and other tumours to be regulated by DNA methylation, proving the global dysregulation of this chromosome in carcinomas [143, 149, 150]. [score:3]
Furthermore, a recent work published the role of miR-376a in the regulation of human dental stem cells [151]. [score:2]
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41
[+] score: 5
miRNA Expressionp-value Expression fold change (log2) Survivalp-value hsa-miR-136 7.52E-14 −1.69 NS hsa-miR-145 5.88E-04 −1.04 0.005 hsa-miR-155 1.18E-21 1.94 NS hsa-miR-181b 5.44E-02 −0.22 NS hsa-miR-342 4.35E-10 −1.25 NS hsa-miR-129 1.29E-16 −3.39 NS hsa-miR-376a 4.35E-07 −0.63 NS hsa-miR-376b 7.37E-02 0.07 NS Survival p-value was calculated from miRNA expression data with Kaplan-Meier analysis. [score:5]
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42
[+] score: 5
Other miRNAs from this paper: hsa-let-7b, hsa-mir-376a-1
HDAC9, a Class II HDAC, represses miR-376a, which downregulates HCC by removing the h3K18 acetylation [33]. [score:4]
Zheng Y. Chen H. Yin M. Ye X. Chen G. Zhou X. Yin L. Zhang C. Ding B. MiR-376a and histone deacetylation 9 form a regulatory circuitry in hepatocellular carcinomaCell Physiol. [score:1]
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43
[+] score: 4
According to the study conducted by Mo and colleagues, human ESCs with low MEG3 expression level (designated as MEG3-OFF) also showed significantly low expressions of DLK1-DIO3 locus-derived noncoding RNAs, including MEG8, miR-127, miR-376, miR-494, miR-495, miR-496, and miR-154, compared to its counterpart MEG3-ON [68]. [score:4]
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44
[+] score: 4
In addition, 17 miRNAs (miR-136, miR-143, miR-148a, miR-15b, miR-18a, miR-181a, miR-181a*, miR-20b, miR-27b, miR-29b, miR-30d, miR-30e*, miR-301a, miR-376a, miR-376b, miR-410 and miR-7), which are differentially expressed in our retinal induction treatment, are involved in the regulation of developing mouse retina 25. [score:4]
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45
[+] score: 4
We have also observed site-specific expression for miR-7, miR-31, miR-107, miR-124, miR-183, miR-339, miR-376a and miR-551a, when comparing supratentorial to infratentorial tumors (Table 2). [score:3]
We performed comparisons between the clinicopathological variables and miRNAs and we identified miR-7, miR-31, miR-107, miR-124a, miR-183, miR-339, miR-376a and miR-551a as supratentorial-specific (Table 2). [score:1]
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46
[+] score: 4
Other miRNAs from this paper: hsa-mir-376a-1
The role of HLA-E in controlling NK cell activity in the context of viral interference could be shown recently by demonstrating how miR-376a(e) regulates HLA-E expression during HCMV infection [40]. [score:4]
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47
[+] score: 4
For example, SNPs that show evidence for regulating the expression of miRNAs in liver include several replicated clinical associations with response to chemotherapeutic agents, including rs9332377 (cisplatin; miR-619) [30] and rs4880 (cyclophosphamide; miR-199a-5p, miR-376a, miR-450a, miR-590-5p) [31]. [score:4]
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48
[+] score: 4
Other miRNAs from this paper: hsa-mir-376a-1, mmu-mir-376a
Wang F., Yu J., Yang G. H., Wang X. S., Zhang J. W. Regulation of erythroid differentiation by miR-376a and its targets. [score:4]
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49
[+] score: 3
The miRNA OpenArray® screen also identified high expression of miR-376a in chondrocytes throughout the human developing limb. [score:3]
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50
[+] score: 3
In this follow up study, we selected nine miRNA candidates (miR-125-3p, miR-320c, miR-320d, miR-9-1, miR-139, miR-125a-5p, miR-4792, miR-376, miR-543, miRNA-381) for validation in the independently recruited patients with early-stage (I, II) colon cancer. [score:1]
MiR-9-1, miR-125a-3p, miR-125a-5p, miR-320c, miR-320d, miR-4792, miR-376, miR-139, miR-543, and miR-381(MS00010752, MS00008554, MS00003423, MS00041867, MS00031710, MS00045087, MS00007392, MS00003493, MS00010080, MS00004116, QIAGEN, Valencia, CA) were selected for downstream validation. [score:1]
In this study, we selected miR-9-1, miR-125a-3p, miR-125a-5p, miR-320c, miR-4792, miR-376, miR-543, and miR-381 as diagnostic candidates for validation. [score:1]
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51
[+] score: 3
miR-485-3p, together with miR-154, miR-299-5p, miR-376a, etc, is mapped to the 14q32.31 region in which allelic deletions [33] and translocations [34] are frequently identified in cancer, suggesting that miR-485-3p may be a tumor suppressor. [score:3]
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52
[+] score: 3
When all of the adults were divided into young (≤ 35 years, n = 32) and middle-aged (> 35 years, n = 28) adults, six miRNAs (hsa-let-7a, miR-30e-5p, miR-107, miR-140, miR-376a, and miR-410) exhibited decreasing expression from young adulthood to middle-aged adulthood according to Benjamini and Hochberg (BH) false discovery rate correction (Table 3). [score:3]
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53
[+] score: 3
For example, miR-144, miR-937, miR-376, miR-519, and miR-548A-3P are shown to regulate a number of mRNAs, and HCK, NFKBIE, IL6, SHMT2, and MCM4 are regulated by several miRNAs. [score:3]
[1 to 20 of 1 sentences]
54
[+] score: 3
It should be noted that the differential expression between grades I and II observed in deep sequencing in a few miRNAs (miR-21, miR-34a, miR-376, miR-451 and miR-99a) were not verified in RT-qPCR (Table 2 and Table 3). [score:3]
[1 to 20 of 1 sentences]
55
[+] score: 3
The first significant study of miRNAs in chondrosarcoma tissue samples and cell lines revealed downregulation of let-7a, miR-100, miR-136, miR-222, miR-335, and miR-376a compared to normal chondrocytes (Yoshitaka et al., 2013; Nugent, 2014). [score:3]
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56
[+] score: 3
For example, only TargetSpy predicted the creation of a ssc-miR-376a site in PPP1R10 and the disruption of a site for ssc-miR-181c in SLA-DRA (Table S4). [score:3]
[1 to 20 of 1 sentences]
57
[+] score: 3
Notably, microRNAs hsa-miR-127-5p, hsa-miR-370 and hsa-miR-376 had been shown to be highly and specifically expressed in islets of developing and adult human pancreas [53, 54]. [score:3]
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58
[+] score: 3
For example, Lee EJ 2007 et al. [44] showed that the miRNAs miR155, miR21, miR222, Let7, miR376a, miR301, miR100, miR125, miR142 and others are overexpressed significantly in human PC. [score:3]
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59
[+] score: 3
With the application of in situ RT-PCR, Lee et al. showed that the aberrantly expressed miR-221, miR-301 and miR-376a were localized to pancreatic cancer cells but not to stroma or normal acini or ducts. [score:3]
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60
[+] score: 2
In addition, a number of other miRNAs, including miR-30d, let-7e, miR-21, miR-9, and miR-376, are also implicated in human pancreatic islet differentiation and development [25, 26, 27]. [score:2]
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61
[+] score: 2
So far, a number of non-coding regulators such as miR-451 (5, 6), miR-23a (7), miR-221/222 (8), miR-376a (9) and miR-223 (10) were reported to play positive or negative roles in controlling erythropoiesis. [score:2]
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62
[+] score: 2
Network 3 functions in cellular growth and proliferation, endocrine system development and function, and protein synthesis, and includes the following gene products: Akt, ANGPTL1, CDKN1B, Ctla2a, DNAJB7, DUT, Dut, ERK, ERK1/2, GAST, GCNT2, HNRPDL, HRSP12, HSPE1, IFNG, IL12, IL12/23R, IL12B, INSRR, Insulin, KHSRP, KLRB1, Mcpt8, MIF, miR-376a/miR-376b/miR-376b-3p, NUTF2, Pkc(s), POMP, PPARA, SLC38A3, SLC5A2, SUMO4, TLR3/4, and VTCN1. [score:2]
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63
[+] score: 2
From the remaining deregulated miRNAs, the most significant were hsa-miR-23/27 cluster and hsa-let-7, hsa-miR-30, and hsa-miR-376 families. [score:2]
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64
[+] score: 2
A similar situation can be found in the human cluster {hsa-mir-368, HP-37, HN-7, hsa-mir-376a} which corresponds to the mouse {mmu-mir-376a, mmu-mir-376b, MP-38}. [score:1]
The fine-grained structure of these loci has some species-specific aspects, as illustrated by Figures 2 and 3. The figures show all the validated miRNAs in these regions, including those with suboptimal prediction scores from the Additional files 7, 8, and 9. We find that some miRNAs that are related in sequence, and have presumably arisen by duplication (such as the mir-368/mir-376-related sequences) have different numbers of copies in rodents and human. [score:1]
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65
[+] score: 2
miR-376a regulates starvation -induced autophagy by controlling of ATG4C and BECN1 transcript and protein levels [27]. [score:2]
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66
[+] score: 2
Kawahara et al. showed that miR-376 transcripts were subject to RNA editing, converting adenosine to inosine in a tissue -dependent manner, leading to a change in the silenced gene set [36]. [score:1]
MiR-376c belongs to the miR-376 cluster gene family, containing miR-376a, miR-376a*, and miR-376b. [score:1]
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67
[+] score: 1
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-18a, hsa-mir-19b-2, hsa-mir-20a, hsa-mir-21, hsa-mir-22, hsa-mir-26a-1, hsa-mir-29a, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-93, hsa-mir-99a, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-106a, hsa-mir-16-2, hsa-mir-197, hsa-mir-199a-1, hsa-mir-148a, hsa-mir-30c-2, hsa-mir-10a, hsa-mir-34a, hsa-mir-182, hsa-mir-199a-2, hsa-mir-205, hsa-mir-210, hsa-mir-221, hsa-mir-223, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-122, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-125b-1, hsa-mir-132, hsa-mir-133a-1, hsa-mir-133a-2, hsa-mir-140, hsa-mir-142, hsa-mir-143, hsa-mir-125b-2, hsa-mir-134, hsa-mir-146a, hsa-mir-150, hsa-mir-206, hsa-mir-155, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-101-2, hsa-mir-130b, hsa-mir-26a-2, hsa-mir-361, hsa-mir-362, hsa-mir-363, hsa-mir-376c, hsa-mir-371a, hsa-mir-375, hsa-mir-376a-1, hsa-mir-378a, hsa-mir-342, hsa-mir-151a, hsa-mir-324, hsa-mir-335, hsa-mir-345, hsa-mir-423, hsa-mir-483, hsa-mir-486-1, hsa-mir-146b, hsa-mir-202, hsa-mir-432, hsa-mir-494, hsa-mir-495, hsa-mir-193b, hsa-mir-497, hsa-mir-455, hsa-mir-545, hsa-mir-487b, hsa-mir-551a, hsa-mir-571, hsa-mir-574, hsa-mir-576, hsa-mir-606, hsa-mir-628, hsa-mir-629, hsa-mir-411, hsa-mir-671, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, hsa-mir-378d-2, hsa-mir-889, hsa-mir-876, hsa-mir-744, hsa-mir-885, hsa-mir-920, hsa-mir-937, hsa-mir-297, hsa-mir-1233-1, hsa-mir-1260a, hsa-mir-664a, hsa-mir-320c-2, hsa-mir-2861, hsa-mir-378b, hsa-mir-1260b, hsa-mir-378c, hsa-mir-1233-2, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-378f, hsa-mir-378g, hsa-mir-378h, hsa-mir-378i, hsa-mir-664b, hsa-mir-378j, hsa-mir-486-2
An miRNA pairwise approach has demonstrated the potential use of two pairs of plasma miRNAs as biomarkers for cognitive-impaired HIV -positive individuals: miR-495-3p in combination with let-7b-5p, miR-151a-5p, or miR-744-5p; and miR-376a-3p/miR-16-5p (211). [score:1]
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68
[+] score: 1
According to miRBase annotation, hsa-mir-1277, hsa-mir-376a-2, hsa-mir-495, hsa-mir-659, hsa-mir-1303, hsa-mir-1307 and so on encode mature miRNA at only their 3p arms. [score:1]
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69
[+] score: 1
This cluster included miR-495, miR-376a, and miR-369-5p. [score:1]
[1 to 20 of 1 sentences]
70
[+] score: 1
For the two other novel bat miRNAs within this cluster (pal-can-411 and pal-can-252), the mature sequences produced non-identical BLAST hits to miR-376 and miR-377, respectively, however the star sequences were 100% identical to miR-376 and miR-377 star sequences, respectively. [score:1]
[1 to 20 of 1 sentences]
71
[+] score: 1
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-17, hsa-mir-21, hsa-mir-29a, hsa-mir-96, mmu-let-7g, mmu-let-7i, mmu-mir-124-3, mmu-mir-140, mmu-mir-181a-2, mmu-mir-182, mmu-mir-183, mmu-mir-194-1, mmu-mir-200b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-181a-1, hsa-mir-200b, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, hsa-let-7g, hsa-let-7i, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-140, hsa-mir-194-1, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-21a, mmu-mir-29a, mmu-mir-96, mmu-mir-34a, mmu-mir-135b, hsa-mir-200c, hsa-mir-181b-2, mmu-mir-17, mmu-mir-200c, mmu-mir-181a-1, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-181b-1, mmu-mir-181c, hsa-mir-194-2, mmu-mir-194-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-376c, hsa-mir-376a-1, mmu-mir-376a, hsa-mir-135b, mmu-mir-181b-2, mmu-mir-376b, dre-mir-34a, dre-mir-181b-1, dre-mir-181b-2, dre-mir-182, dre-mir-183, dre-mir-181a-1, dre-let-7a-1, dre-let-7a-2, dre-let-7a-3, dre-let-7a-4, dre-let-7a-5, dre-let-7a-6, dre-let-7b, dre-let-7c-1, dre-let-7c-2, dre-let-7d-1, dre-let-7d-2, dre-let-7e, dre-let-7f, dre-let-7g-1, dre-let-7g-2, dre-let-7h, dre-let-7i, dre-mir-15a-1, dre-mir-15a-2, dre-mir-17a-1, dre-mir-17a-2, dre-mir-21-1, dre-mir-21-2, dre-mir-29a, dre-mir-96, dre-mir-124-1, dre-mir-124-2, dre-mir-124-3, dre-mir-124-4, dre-mir-124-5, dre-mir-124-6, dre-mir-140, dre-mir-181c, dre-mir-194a, dre-mir-194b, dre-mir-200b, dre-mir-200c, hsa-mir-376b, hsa-mir-181d, hsa-mir-507, dre-let-7j, dre-mir-135b, dre-mir-181a-2, mmu-mir-376c, dre-mir-34b, dre-mir-34c, mmu-mir-181d, mmu-mir-21b, mmu-let-7j, mmu-mir-21c, mmu-let-7k, dre-mir-181a-4, dre-mir-181a-3, dre-mir-181a-5, dre-mir-181b-3, dre-mir-181d, mmu-mir-124b
Analysis of miR-376 RNA cluster members in the mouse inner ear. [score:1]
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72
[+] score: 1
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-17, hsa-mir-19a, hsa-mir-21, hsa-mir-31, hsa-mir-92a-1, hsa-mir-92a-2, hsa-mir-105-1, hsa-mir-105-2, hsa-mir-199a-1, hsa-mir-34a, hsa-mir-187, hsa-mir-199a-2, hsa-mir-205, hsa-mir-214, hsa-mir-221, hsa-let-7g, hsa-let-7i, hsa-mir-128-1, hsa-mir-141, hsa-mir-144, hsa-mir-145, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-146a, hsa-mir-200c, hsa-mir-128-2, hsa-mir-29c, hsa-mir-376a-1, hsa-mir-378a, hsa-mir-133b, hsa-mir-429, hsa-mir-487a, hsa-mir-515-1, hsa-mir-515-2, hsa-mir-526b, hsa-mir-514a-1, hsa-mir-514a-2, hsa-mir-514a-3, hsa-mir-548a-1, hsa-mir-548b, hsa-mir-548a-2, hsa-mir-548a-3, hsa-mir-548c, hsa-mir-548d-1, hsa-mir-548d-2, hsa-mir-656, hsa-mir-542, hsa-mir-378d-2, hsa-mir-548e, hsa-mir-548j, hsa-mir-548k, hsa-mir-548l, hsa-mir-548f-1, hsa-mir-548f-2, hsa-mir-548f-3, hsa-mir-548f-4, hsa-mir-548f-5, hsa-mir-548g, hsa-mir-548n, hsa-mir-548m, hsa-mir-548o, hsa-mir-548h-1, hsa-mir-548h-2, hsa-mir-548h-3, hsa-mir-548h-4, hsa-mir-1275, hsa-mir-548p, hsa-mir-548i-1, hsa-mir-548i-2, hsa-mir-548i-3, hsa-mir-548i-4, hsa-mir-2114, hsa-mir-548q, hsa-mir-548s, hsa-mir-378b, hsa-mir-548t, hsa-mir-548u, hsa-mir-548v, hsa-mir-548w, hsa-mir-548x, hsa-mir-514b, hsa-mir-378c, hsa-mir-4303, hsa-mir-4309, hsa-mir-4307, hsa-mir-4278, hsa-mir-548y, hsa-mir-548z, hsa-mir-548aa-1, hsa-mir-548aa-2, hsa-mir-548o-2, hsa-mir-378d-1, hsa-mir-378e, hsa-mir-548h-5, hsa-mir-548ab, hsa-mir-378f, hsa-mir-378g, hsa-mir-548ac, hsa-mir-548ad, hsa-mir-548ae-1, hsa-mir-548ae-2, hsa-mir-548ag-1, hsa-mir-548ag-2, hsa-mir-548ah, hsa-mir-378h, hsa-mir-548ai, hsa-mir-548aj-1, hsa-mir-548aj-2, hsa-mir-548x-2, hsa-mir-548ak, hsa-mir-548al, hsa-mir-378i, hsa-mir-548am, hsa-mir-548an, hsa-mir-548ao, hsa-mir-548ap, hsa-mir-548aq, hsa-mir-548ar, hsa-mir-548as, hsa-mir-548at, hsa-mir-548au, hsa-mir-548av, hsa-mir-548aw, hsa-mir-548ax, hsa-mir-378j, hsa-mir-548ay, hsa-mir-548az, hsa-mir-548ba, hsa-mir-548bb, hsa-mir-548bc
The accumulation of unedited has-miR-376a* was associated with glioma tumor metastasis and promoted cell migration and invasions [27]. [score:1]
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[+] score: 1
Other miRNAs from this paper: hsa-let-7a-1, hsa-let-7a-2, hsa-let-7a-3, hsa-let-7b, hsa-let-7c, hsa-let-7d, hsa-let-7e, hsa-let-7f-1, hsa-let-7f-2, hsa-mir-15a, hsa-mir-16-1, hsa-mir-17, hsa-mir-20a, hsa-mir-23a, hsa-mir-24-1, hsa-mir-24-2, hsa-mir-26a-1, hsa-mir-26b, hsa-mir-29a, hsa-mir-30a, hsa-mir-93, hsa-mir-101-1, hsa-mir-29b-1, hsa-mir-29b-2, hsa-mir-107, hsa-mir-16-2, mmu-let-7g, mmu-let-7i, mmu-mir-15b, mmu-mir-23b, mmu-mir-29b-1, mmu-mir-30a, mmu-mir-30b, mmu-mir-101a, mmu-mir-124-3, mmu-mir-125a, mmu-mir-130a, mmu-mir-9-2, mmu-mir-135a-1, mmu-mir-136, mmu-mir-138-2, mmu-mir-140, mmu-mir-144, mmu-mir-145a, mmu-mir-146a, mmu-mir-149, mmu-mir-152, mmu-mir-10b, mmu-mir-181a-2, mmu-mir-182, mmu-mir-183, mmu-mir-185, mmu-mir-24-1, mmu-mir-191, mmu-mir-193a, mmu-mir-195a, mmu-mir-200b, mmu-mir-204, hsa-mir-30c-2, hsa-mir-30d, mmu-mir-30e, hsa-mir-7-1, hsa-mir-7-2, hsa-mir-7-3, hsa-mir-10a, hsa-mir-10b, hsa-mir-34a, hsa-mir-181a-2, hsa-mir-181b-1, hsa-mir-181c, hsa-mir-182, hsa-mir-183, hsa-mir-204, hsa-mir-181a-1, hsa-mir-221, hsa-mir-222, hsa-mir-200b, mmu-mir-301a, mmu-mir-34c, mmu-mir-34b, mmu-let-7d, mmu-mir-130b, hsa-let-7g, hsa-let-7i, hsa-mir-15b, hsa-mir-23b, hsa-mir-30b, hsa-mir-124-1, hsa-mir-124-2, hsa-mir-124-3, hsa-mir-130a, hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-138-2, hsa-mir-140, hsa-mir-144, hsa-mir-145, hsa-mir-152, hsa-mir-191, hsa-mir-9-1, hsa-mir-9-2, hsa-mir-9-3, hsa-mir-125a, hsa-mir-136, hsa-mir-138-1, hsa-mir-146a, hsa-mir-149, hsa-mir-185, hsa-mir-193a, hsa-mir-195, hsa-mir-320a, mmu-mir-30c-1, mmu-mir-30c-2, mmu-mir-30d, mmu-let-7a-1, mmu-let-7a-2, mmu-let-7b, mmu-let-7c-1, mmu-let-7c-2, mmu-let-7e, mmu-let-7f-1, mmu-let-7f-2, mmu-mir-15a, mmu-mir-16-1, mmu-mir-16-2, mmu-mir-20a, mmu-mir-23a, mmu-mir-24-2, mmu-mir-26a-1, mmu-mir-26b, mmu-mir-29a, mmu-mir-29c, mmu-mir-93, mmu-mir-34a, mmu-mir-330, mmu-mir-339, mmu-mir-340, mmu-mir-135b, mmu-mir-101b, hsa-mir-200c, hsa-mir-181b-2, mmu-mir-107, mmu-mir-10a, mmu-mir-17, mmu-mir-200c, mmu-mir-181a-1, mmu-mir-320, mmu-mir-26a-2, mmu-mir-221, mmu-mir-222, mmu-mir-29b-2, mmu-mir-135a-2, mmu-mir-124-1, mmu-mir-124-2, mmu-mir-9-1, mmu-mir-9-3, mmu-mir-138-1, mmu-mir-181b-1, mmu-mir-181c, mmu-mir-7a-1, mmu-mir-7a-2, mmu-mir-7b, hsa-mir-29c, hsa-mir-30c-1, hsa-mir-101-2, hsa-mir-34b, hsa-mir-34c, hsa-mir-301a, hsa-mir-130b, hsa-mir-30e, hsa-mir-26a-2, hsa-mir-361, mmu-mir-361, hsa-mir-376a-1, mmu-mir-376a, hsa-mir-340, hsa-mir-330, hsa-mir-135b, hsa-mir-339, hsa-mir-335, mmu-mir-335, mmu-mir-181b-2, mmu-mir-376b, mmu-mir-434, mmu-mir-467a-1, hsa-mir-376b, hsa-mir-485, hsa-mir-146b, hsa-mir-193b, hsa-mir-181d, mmu-mir-485, mmu-mir-541, hsa-mir-320b-1, hsa-mir-320c-1, hsa-mir-320b-2, mmu-mir-301b, mmu-mir-674, mmu-mir-146b, mmu-mir-467b, mmu-mir-669c, mmu-mir-708, mmu-mir-676, mmu-mir-181d, mmu-mir-193b, mmu-mir-467c, mmu-mir-467d, hsa-mir-541, hsa-mir-708, hsa-mir-301b, mmu-mir-467e, mmu-mir-467f, mmu-mir-467g, mmu-mir-467h, hsa-mir-320d-1, hsa-mir-320c-2, hsa-mir-320d-2, mmu-mir-467a-2, mmu-mir-467a-3, mmu-mir-467a-4, mmu-mir-467a-5, mmu-mir-467a-6, mmu-mir-467a-7, mmu-mir-467a-8, mmu-mir-467a-9, mmu-mir-467a-10, hsa-mir-320e, hsa-mir-676, mmu-mir-101c, mmu-mir-195b, mmu-mir-145b, mmu-let-7j, mmu-mir-130c, mmu-mir-30f, mmu-let-7k, mmu-mir-9b-2, mmu-mir-124b, mmu-mir-9b-1, mmu-mir-9b-3
50E-0367mmu-miR-339-5pmir-3390.206.807.92E-037.53E-028mmu-miR-34c-5pmir-340.246.689.54E-066.88E-0477mmu-miR-34a-5pmir-340.179.541.17E-029.66E-0245mmu-miR-340-5pmir-3400.178.511.71E-032.45E-0217mmu-miR-361-5pmir-3610.247.887.74E-052.90E-0319mmu-miR-376b-3pmir-3680.268.451.05E-043.50E-0356mmu-miR-376a-3pmir-3680.1910.215.63E-036.40E-0223mmu-miR-434-3pmir-4340.2210.461.76E-044. [score:1]
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48) and miR-376a (ref. [score:1]
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Additionally, this viral miRNA was found to act synergistically with another cellular miRNA, hsa-miR-376a. [score:1]
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Note that, for consistency, we refer to orthologous miRNAs according to how they are annotated in humans, for example, we use miR-376a-1 to denote both the human miRNA hsa-miR-376a-1 and the mouse miRNA mmu-miR-376a*. [score:1]
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964.00E-04 hsa-miR-376a−1.831.00E-03 hsa-miR-2101.877.00E-04 hsa-miR-628−1.871.00E-03 hsa-miR-17-3p1.879.00E-04 hsa-miR-487b−1.951.00E-03 hsa-miR-302b*1.769.00E-04 hsa-miR-410−1.811.00E-03 hsa-miR-2241.599.00E-04 hsa-miR-140−1.792.00E-03 hsa-miR-1831.789.00E-04 hsa-miR-801−1.342.00E-03 hsa-miR-1381.791.00E-03 hsa-miR-376a*−1.802.00E-03 hsa-miR-1881.632.00E-03 hsa-miR-154−1.763.00E-03 hsa-miR-92b1. [score:1]
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Five possible miRs (miR-200c-3p, miR-200b-3p, miR-429, miR-376a-3p, and miR-376b-3p) were identified, using the Starbase human Pan cancer tool, that could interact with the hsa-circ-0001358 [92]. [score:1]
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We checked the reference suggested by the reviewer and found that they have talked about only one family within the cluster of miR-376 (miR-376a, -b or-c). [score:1]
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